liu.seSearch for publications in DiVA
Change search
Refine search result
1 - 14 of 14
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Danielsson, Anna
    et al.
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Fagerholm, Siri
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Öst, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Franck, Niclas
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences.
    Kjölhede, Preben
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Nyström, Fredrik H
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Short-Term Overeating Induces Insulin Resistance in Fat Cells in Lean Human Subjects2009In: Molecular medicine (Cambridge, Mass. Print), ISSN 1076-1551, E-ISSN 1528-3658, Vol. 15, no 7-8, p. 228-234Article in journal (Refereed)
    Abstract [en]

    Insulin resistance and type 2 diabetes (T2D) are closely linked to obesity. Numerous prospective studies have reported on weight gain, insulin resistance, and insulin signaling in experimental animals, but not in humans. We examined insulin signaling in adipocytes from lean volunteers, before and at the end of a 4-wk period of consuming a fast-food, high-calorie diet that led to weight gain. We also examined adipocytes from patients with T2D. During the high-calorie diet, subjects gained 10% body weight and 19% total body fat, but stayed lean (body mass index = 24.3 kg/m2) and developed moderate systemic insulin resistance. Similarly to the situation in T2D subjects, in subjects on the high-calorie diet, the amount of insulin receptors was reduced and phosphorylation of IRS1 at tyrosine and at serine-307 (human sequence, corresponding to murine serine-302) were impaired. The amount of insulin receptor substrate protein-1 (IRS1) and the phosphorylation of IRS1 at serine-312 (human sequence, corresponding to murine serine-307) were unaffected by the diet. Unlike the T2D subjects, in subjects on the high-calorie diet, likely owing to the ongoing weight-gain, phosphorylation of MAP-kinases ERK1/2 became hyperresponsive to insulin. To our knowledge this study is the first to investigate insulin signaling during overeating in humans, and it demonstrates that T2D effects on intracellular insulin signaling already occur after 4 wks of a high-calorie diet and that the effects in humans differ from those in laboratory animals.

  • 2.
    Franck, Niclas
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    On the importance of fat cell size, location and signaling in insulin resistance2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Obesity has reached epidemic proportions worldwide and is associated with insulin resistance, type 2 diabetes and cardiovascular disease. During the past decades, substantial evidence has demonstrated that not only the amount of adipose tissue constitutes a major determinant in the development of metabolic disorders, but also the distribution. The visceral adipose tissue has shown to be stronger correlated with insulin resistance, type 2 diabetes and cardiovascular disease than the subcutaneous depot. When we measured the activity of the nuclear receptor PPARγ in visceral and subcutaneous adipocytes, we found considerably lower activity in fat cells obtained from the visceral portion. This finding provides additional evidence to the unfavorable consequences of visceral obesity. The common PPARγ polymorphism Pro12Ala was studied in type 2 diabetic patients. We found that men with the Ala isoform exhibited higher sagittal abdominal diameter, waist circumference and body weight compared with homozygotes for the Pro isoform. However, no differences in either gender with regard to blood pressure or markers of cardiovascular disease and organ damage could be observed.

    In addition to an excessive visceral adipose tissue mass, obese subjects with enlarged adipocytes display an increased risk for developing metabolic disorders compared with individuals exhibiting smaller fat cells but a similar degree of adiposity. The insulin responsiveness in small and large adipocytes obtained from the same subject was examined. Upon insulin stimulation, we found approximately a 2 fold increase of GLUT4 at the plasma membrane in small adipocytes, whereas the large fat cells were refractory to insulin induced GLUT4 translocation. This finding demonstrates a causal relationship between the accumulation of large fat cells in obese subjects and reduced insulin responsiveness.

    Caloric restriction in humans ameliorates insulin responsiveness in liver and muscle prior to any substantial weight loss. By combining gene expression profiles of adipose tissue and adipocytes from human subjects undergoing either caloric restriction or overfeeding, we identified genes regulated by changes in caloric intake independent of weight loss per se. We found several genes under the control of mTOR and SREBP1 as well as genes involved in β-oxidation, liberation of fatty acids and glyceroneogenesis to be regulated during the interventions. These genes may indicate pathways and mechanisms mediating the effects of nutrient deprivation and obesity on morbidity and mortality.

    List of papers
    1. Peroxisome proliferator activated receptor gamma activity is low in mature primary human visceral adipocytes
    Open this publication in new window or tab >>Peroxisome proliferator activated receptor gamma activity is low in mature primary human visceral adipocytes
    Show others...
    2007 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 1, p. 195-201Article in journal (Refereed) Published
    Abstract [en]

    AIMS/HYPOTHESIS: The amount of visceral fat mass strongly relates to insulin resistance in humans. The transcription factor peroxisome proliferator activated receptor gamma (PPARG) is abundant in adipocytes and regulates genes of importance for insulin sensitivity. Our objective was to study PPARG activity in human visceral and subcutaneous adipocytes and to compare this with the most common model for human disease, the mouse.

    MATERIALS AND METHODS: We transfected primary human adipocytes with a plasmid encoding firefly luciferase controlled by PPARG response element (PPRE) from the acyl-CoA-oxidase gene and measured PPRE activity by emission of light. RESULTS: We found that PPRE activity was 6.6-fold higher (median) in adipocytes from subcutaneous than from omental fat from the same subjects (n = 23). The activity was also 6.2-fold higher in subcutaneous than in intra-abdominal fat cells when we used a PPARG ligand-binding domain-GAL4 fusion protein as reporter, demonstrating that the difference in PPRE activity was due to different levels of activity of the PPARG receptor in the two fat depots. Stimulation with 5 micromol/l rosiglitazone did not induce a PPRE activity in visceral adipocytes that was as high as basal levels in subcutaneous adipocytes. Interestingly, in mice of two different strains the PPRE activity was similar in visceral and subcutaneous fat cells.

    CONCLUSIONS/INTERPRETATION: We found considerably lower PPARG activity in visceral than in subcutaneous primary human adipocytes. Further studies of the molecular mechanisms behind this difference could lead to development of drugs that target the adverse effects of visceral obesity.

    Keywords
    x-ray, vibrational, spectrum, Hartree-Fock, static exchange, Franck-Condon
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-18462 (URN)10.1007/s00125-006-0515-x (DOI)000243188000026 ()17106695 (PubMedID)
    Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2019-06-28Bibliographically approved
    2. Insulin-induced GLUT4 translocation to the plasma membrane is blunted in large compared with small primary fat cells isolated from the same individual
    Open this publication in new window or tab >>Insulin-induced GLUT4 translocation to the plasma membrane is blunted in large compared with small primary fat cells isolated from the same individual
    Show others...
    2007 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 8, p. 1716-1722Article in journal (Refereed) Published
    Abstract [en]

    Aims/hypothesis: Several studies have suggested that large fat cells are less responsive to insulin than small fat cells. However, in these studies, large fat cells from obese individuals were compared with smaller fat cells from leaner participants, in effect making it impossible to draw conclusions about whether there is a causal relationship between fat cell size and insulin sensitivity. We hypothesised that small fat cells might be more insulin-responsive than large adipocytes when obtained from the same individual.

    Materials and methods: We developed a method of sorting isolated primary human fat cells by using nylon filters of two different pore sizes. The cells were stained to visualise DNA, which allowed discrimination from artefacts such as lipid droplets. The sorted cells were left to recover overnight, since we had previously demonstrated that this is necessary for correct assessment of insulin response.

    Results: We found similar amounts of the insulin receptor (IR), IRS-1 and GLUT4 when we compared small and large adipocytes from the same volunteer by immunoblotting experiments using the same total cell volume from both cell populations. Activation of IR, IRS-1 and Akt1 (also known as protein kinase B) by insulin was similar in the two cell populations. However, immunofluorescence confocal microscopy of plasma membrane sheets did not reveal any increase in the amount of GLUT4 in the plasma membrane following insulin stimulation in the large fat cells, whereas we saw a twofold increase in the amount of GLUT4 in the small fat cells.

    Conclusions/interpretation: Our results support a causal relationship between the accumulation of large fat cells in obese individuals and reduced insulin responsiveness.

    Keywords
    Adipocyte, GLUT4, Human, Insulin, Insulin receptor, Insulin resistance, IRS-1, Primary fat cell
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14541 (URN)10.1007/s00125-007-0713-1 (DOI)
    Available from: 2007-06-01 Created: 2007-06-01 Last updated: 2017-12-13Bibliographically approved
    3. Identification of adipocyte genes regulated by caloric intake
    Open this publication in new window or tab >>Identification of adipocyte genes regulated by caloric intake
    Show others...
    2011 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 96, no 2, p. E413-E418Article in journal (Refereed) Published
    Abstract [en]

    CONTEXT: Changes in energy intake have marked and rapid effects on metabolic functions and some of the effects may be due to changes in adipose tissue gene expression that precede alterations in body weight.

    OBJECTIVE: To identify genes in adipose tissue regulated by changes in caloric intake independent of changes in body weight.

    RESEARCH DESIGN AND METHODS: Obese subjects were given a very-low calorie diet (VLCD; 450 kcal/day) for 16 weeks. After the diet, ordinary food was gradually reintroduced during 2 weeks while there were minimal changes in body weight. Adipose tissue gene expression was measured by microarray analysis. First, genes regulated during caloric restriction and in the opposite direction during the weight stable re-feeding phase were identified. To verify opposite regulation to that observed during caloric restriction, identified genes were further analyzed using adipocyte expression profiles from healthy subjects before and after overfeeding. Results were confirmed using real time PCR or immunoassay.

    RESULTS: Using a significance level of p<0.05 for all comparisons, 52 genes were downregulated and 50 were up-regulated by caloric restriction and regulated in the opposite direction by re-feeding and overfeeding. Among these were genes that affect lipogenesis (ACLY, ACACA, FASN, SCD), protein synthesis (4EBP1, 4EBP2), beta-oxidation (CPT1B), liberation of fatty acids (CIDEA) and glyceroneogenesis (PCK2). Interestingly, several of these are under control of the master regulator mTOR.

    CONCLUSIONS: The observed transcriptional changes indicate that mTOR plays a central role in the control of diet-regulated adipocyte genes involved in lipogenesis and protein synthesis.

    Place, publisher, year, edition, pages
    Endocrine society, 2011
    Keywords
    Obesity, DNA microarray, caloric restriction, overfeeding, adipose tissue
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-18464 (URN)10.1210/jc.2009-2534 (DOI)000286972500025 ()
    Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2018-10-08Bibliographically approved
    4. The Ala isoform of the PPARγ Pro12Ala polymorphism is related to increased abdominal obesity in men but has little impact on cardiovascular risk markers in patients with type 2 diabetes
    Open this publication in new window or tab >>The Ala isoform of the PPARγ Pro12Ala polymorphism is related to increased abdominal obesity in men but has little impact on cardiovascular risk markers in patients with type 2 diabetes
    Show others...
    2009 (English)Article in journal (Other academic) Submitted
    Abstract [en]

    Background: The interaction of the PPARγ Pro12Ala with obesity and cardiovascular risk is controversial. We aimed to study potential associations of the Ala isoform of this polymorphism with obesity, blood pressure and markers of cardiovascular disease and organ damage in middle aged patients with type 2 diabetes.

    Subjects and methods: We recruited 148 women and 246 men in the CArdiovascular Risk factors in Patients with DIabetes – a Prospective study in the Primary health care setting (CARDIPP) study in which early markers of organ damage by cardiac echocardiography, determination of carotid intima media thickness (IMT) and measurement of pulse wave velocity (PWV) was performed. Blood pressures were measured as both as 24-hour ambulatory blood pressure and as a noninvasive recording of central blood pressure. Allelic discrimination was detected with the ABI prism 7500HT Sequence Detection System. Due to the low prevalence of Ala homozygotes, heterozygotes and homozygotes of Ala were defined as Ala isoform in the analyses.

    Results: Men with Ala isoform exhibited higher sagittal abdominal diameter (Pro: 25.4±3.4 cm, Ala: 26.7±4.9 cm, p= 0.04) waist circumference (Pro: 104±11 cm, Ala: 108±15 cm, p= 0.046) and body weight (Pro: 91.6±14, Ala: 96.5±18, p= 0.035) than homozygotes for the Pro isoform. However, there were no differences in either gender with respect to blood pressures, left-ventricular mass-index, carotid IMT or carotid-femoral PWV in the participants.

    Conclusion: It is unlikely that determination of the PPARγ Pro12Ala isoform in clinic practice adds any major information on cardiovascular risk or circulatory organ damage in patients with type 2 diabetes.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-18465 (URN)
    Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2017-03-27Bibliographically approved
  • 3.
    Franck, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Gummesson, Anders
    Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Jernås, Margareta
    Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Guillot, Gilles
    Department of Mathematical Statistics, Chalmers University of Technology and University of Gothenburg, Gothenburg, Sweden; Applied Mathematics and Computer Sciences Department,National Research Institute for Agronomy, Paris, France; Centre for Ecology and Evolutionary Synthesis, Department of Biology, University of Oslo, Oslo, Norway.
    Glad, Camilla
    Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Svensson, Per-Arne
    Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden;.
    Rudemo, Mats
    Department of Mathematical Statistics, Chalmers University of Technology and University of Gothenburg, Gothenburg, Sweden.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Carlsson, Lena M. S.
    Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Olsson, Bob
    Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Identification of adipocyte genes regulated by caloric intake2011In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 96, no 2, p. E413-E418Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Changes in energy intake have marked and rapid effects on metabolic functions and some of the effects may be due to changes in adipose tissue gene expression that precede alterations in body weight.

    OBJECTIVE: To identify genes in adipose tissue regulated by changes in caloric intake independent of changes in body weight.

    RESEARCH DESIGN AND METHODS: Obese subjects were given a very-low calorie diet (VLCD; 450 kcal/day) for 16 weeks. After the diet, ordinary food was gradually reintroduced during 2 weeks while there were minimal changes in body weight. Adipose tissue gene expression was measured by microarray analysis. First, genes regulated during caloric restriction and in the opposite direction during the weight stable re-feeding phase were identified. To verify opposite regulation to that observed during caloric restriction, identified genes were further analyzed using adipocyte expression profiles from healthy subjects before and after overfeeding. Results were confirmed using real time PCR or immunoassay.

    RESULTS: Using a significance level of p<0.05 for all comparisons, 52 genes were downregulated and 50 were up-regulated by caloric restriction and regulated in the opposite direction by re-feeding and overfeeding. Among these were genes that affect lipogenesis (ACLY, ACACA, FASN, SCD), protein synthesis (4EBP1, 4EBP2), beta-oxidation (CPT1B), liberation of fatty acids (CIDEA) and glyceroneogenesis (PCK2). Interestingly, several of these are under control of the master regulator mTOR.

    CONCLUSIONS: The observed transcriptional changes indicate that mTOR plays a central role in the control of diet-regulated adipocyte genes involved in lipogenesis and protein synthesis.

  • 4.
    Franck, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Åstrand, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Lindström, Torbjön
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Cardiovascular risk factors related to the PPARγ Pro12Ala polymorphism in patients with type 2 diabetes are gender dependent2012In: Blood Pressure, ISSN 0803-7051, E-ISSN 1651-1999, Vol. 21, no 2, p. 122-127Article in journal (Refereed)
    Abstract [en]

    The interaction of the PPARγ Pro12Ala polymorphism with diabetes and cardiovascular risk is controversial. We studied 173 women and 309 men in the observational CARDIPP trial in which determination of left ventricular mass, carotid intima-media thickness (IMT) and pulse wave velocity (PWV) were performed. Blood pressures were measured with 24-h ambulatory technique (ABP). Heterozygotes and homozygotes of Ala were defined as Ala in the analyses. Men with Ala-isoform displayed higher waist circumference (Ala: 107 ± 14 cm, Pro: 104 ± 11 cm, p = 0.045) and body weight (Ala: 95.7 ± 18 kg, Pro: 91.6 ± 14 kg, p = 0.042) than Pro-homozygotes. Men with ALA-isoform also showed higher systolic ABP levels (Ala: 134 ± 15 mmHg, Pro: 130 ± 14 mmHg, p = 0.004), whereas left ventricular mass index, IMT and PWV were unrelated to isoforms. In contrast, carotid–radial PWV was lower in women with the Ala-isoform (Ala: 7.9 ± 1.0 m/s, Pro: 8.5 ± 1.3 m/s, p = 0.01) and levels of apolipoprotein A1 were higher (Ala: 1.43 ± 0.27 g/l, Pro: 1.35 ± 0.17 g/l, p = 0.03). In conclusion, we found that men with type 2 diabetes having the Ala-isoform of PPARγ Pro12Ala had an unfavorable cardiovascular risk profile, whereas women with this isoform had lower carotid–radial PWV and higher apolipoprotein A1 levels suggesting a beneficial prognosis. These differences according to gender of the ALA isoform in type 2 diabetes deserve further attention.

  • 5.
    Franck, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Åstrand, Olov
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    The Ala isoform of the PPARγ Pro12Ala polymorphism is related to increased abdominal obesity in men but has little impact on cardiovascular risk markers in patients with type 2 diabetes2009Article in journal (Other academic)
    Abstract [en]

    Background: The interaction of the PPARγ Pro12Ala with obesity and cardiovascular risk is controversial. We aimed to study potential associations of the Ala isoform of this polymorphism with obesity, blood pressure and markers of cardiovascular disease and organ damage in middle aged patients with type 2 diabetes.

    Subjects and methods: We recruited 148 women and 246 men in the CArdiovascular Risk factors in Patients with DIabetes – a Prospective study in the Primary health care setting (CARDIPP) study in which early markers of organ damage by cardiac echocardiography, determination of carotid intima media thickness (IMT) and measurement of pulse wave velocity (PWV) was performed. Blood pressures were measured as both as 24-hour ambulatory blood pressure and as a noninvasive recording of central blood pressure. Allelic discrimination was detected with the ABI prism 7500HT Sequence Detection System. Due to the low prevalence of Ala homozygotes, heterozygotes and homozygotes of Ala were defined as Ala isoform in the analyses.

    Results: Men with Ala isoform exhibited higher sagittal abdominal diameter (Pro: 25.4±3.4 cm, Ala: 26.7±4.9 cm, p= 0.04) waist circumference (Pro: 104±11 cm, Ala: 108±15 cm, p= 0.046) and body weight (Pro: 91.6±14, Ala: 96.5±18, p= 0.035) than homozygotes for the Pro isoform. However, there were no differences in either gender with respect to blood pressures, left-ventricular mass-index, carotid IMT or carotid-femoral PWV in the participants.

    Conclusion: It is unlikely that determination of the PPARγ Pro12Ala isoform in clinic practice adds any major information on cardiovascular risk or circulatory organ damage in patients with type 2 diabetes.

  • 6.
    Franck, Niclas
    et al.
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences.
    Stenkula, Karin G.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik H.
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences.
    Öst, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Insulin-induced GLUT4 translocation to the plasma membrane is blunted in large compared with small primary fat cells isolated from the same individual2007In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 8, p. 1716-1722Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Several studies have suggested that large fat cells are less responsive to insulin than small fat cells. However, in these studies, large fat cells from obese individuals were compared with smaller fat cells from leaner participants, in effect making it impossible to draw conclusions about whether there is a causal relationship between fat cell size and insulin sensitivity. We hypothesised that small fat cells might be more insulin-responsive than large adipocytes when obtained from the same individual.

    Materials and methods: We developed a method of sorting isolated primary human fat cells by using nylon filters of two different pore sizes. The cells were stained to visualise DNA, which allowed discrimination from artefacts such as lipid droplets. The sorted cells were left to recover overnight, since we had previously demonstrated that this is necessary for correct assessment of insulin response.

    Results: We found similar amounts of the insulin receptor (IR), IRS-1 and GLUT4 when we compared small and large adipocytes from the same volunteer by immunoblotting experiments using the same total cell volume from both cell populations. Activation of IR, IRS-1 and Akt1 (also known as protein kinase B) by insulin was similar in the two cell populations. However, immunofluorescence confocal microscopy of plasma membrane sheets did not reveal any increase in the amount of GLUT4 in the plasma membrane following insulin stimulation in the large fat cells, whereas we saw a twofold increase in the amount of GLUT4 in the small fat cells.

    Conclusions/interpretation: Our results support a causal relationship between the accumulation of large fat cells in obese individuals and reduced insulin responsiveness.

  • 7.
    Kos, Katrina
    et al.
    Aintree University Hospital.
    Wong, Steve
    Aintree University Hospital.
    Tan, Bee
    University of Warwick.
    Gummesson, Anders
    University of Gothenburg.
    Jernas, Margareta
    University of Gothenburg.
    Franck, Niclas
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Kerrigan, David
    Aintree University Hospital.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Carlsson, Lena M S
    University of Gothenburg.
    Randeva, Harpal S
    University of Warwick.
    Pinkney, Jonathan H
    Peninsula Medical School.
    Wilding, John P H
    Aintree University Hospital.
    Regulation of the Fibrosis and Angiogenesis Promoter SPARC/Osteonectin in Human Adipose Tissue by Weight Change, Leptin, Insulin, and Glucose2009In: DIABETES, ISSN 0012-1797, Vol. 58, no 8, p. 1780-1788Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-Matricellular Secreted Protein, Acidic and Rich in Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose tissue collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human adipose tissue is influenced by glucose metabolism and adipokines. RESEARCH DESIGN AND METHODS-Serum and adipose tissue biopsies were obtained from morbidly obese nondiabetic subjects undergoing bariatric surgery and lean control subjects for analysis of metabolic markers, SPARC, and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet of 1,883 kJ (450 kcal)/day for 16 weeks and serial subcutaneous-abdominal-adipose tissue (SCAT) biopsies (weight loss: 28 +/- 3.7 kg). Another six lean subjects underwent fast-food-based hyperalimentation for 4 weeks (weight gain: 7.2 +/- 1.6 kg). Finally, visceral adipose tissue explants were cultured with recombinant leptin, insulin, and glucose, and SPARC mRNA and protein expression determined by Western blot analyses. RESULTS-SPARC expression in human adipose tissue correlated with fat mass and was higher in SCAT. Weight, loss induced by very-low-calorie diet lowered SPARC expression by 33% and increased by 30% in adipose tissue of subjects gaining weight after a fast-food diet. SPARC expression was correlated with leptin independent of fat mass and correlated with homeostasis model assessment-insulin resistance. In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein. CONCLUSIONS-Our data suggest that SPARC Expression is predominant in subcutaneous fat and its expression and secretion in adipose tissue are influenced by fat mass, leptin, insulin, and glucose. The profibrotic effects of SPARC may contribute to metabolic dysregulation in obesity.

  • 8.
    McCulloch, Laura J
    et al.
    University of Exeter Medical School, Exeter, UK.
    Rawling, Tom J
    University of Exeter Medical School, Exeter, UK.
    Sjöholm, Kajsa
    The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Franck, Niclas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Dankel, Simon N
    University of Bergen and Hormone Laboratory, Haukeland University Hospital, Norway.
    Price, Emily J
    University of Exeter Medical School, Exeter, UK.
    Knight, Bridget
    University of Exeter Medical School, UK.
    Liversedge, Neil H
    Royal Devon and Exeter NHS Foundation Trust, UK.
    Mellgren, Gunnar
    University of Bergen and Hormone Laboratory, Haukeland University Hospital, Norway.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Carlsson, Lena M
    The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Kos, Katarina
    University of Exeter Medical School, Exeter, UK.
    COL6A3 is regulated by leptin in human adipose tissue and reduced in obesity2015In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 156, no 1, p. 134-146Article in journal (Refereed)
    Abstract [en]

    Fibrosis of adipose tissue (AT) increases AT rigidity, reduces its expandability and contributes to metabolic dysfunction. Collagen type VI, alpha3 (COL6A3) encodes one subunit of a fibrotic extracellular matrix (ECM) protein highly expressed in rodent AT. Knock-out of collagen VI in rodent AT led to a significant improvement in metabolic health in obese, diabetic (ob/ob) mice however, it is unknown whether this collagen has the same metabolic significance in human AT. We therefore aimed to undertake a comprehensive assessment of COL6A3 in relation to human AT and obesity. Characterisation of COL6A3 in human AT showed 5 fold higher expression in the stromalvascular fraction compared with adipocyte expression and significantly higher expression in subcutaneous than omental AT. In both depots COL6A3 expression appeared to be lowered in obesity, whilst diet and surgery-induced weight loss increased COL6A3 expression in subcutaneous AT. Leptin treatment caused a dose dependent decrease in COL6A3 expression although no effect was seen with insulin or glucose treatment and no difference observed in subjects with diabetes. In addition, we found that the collagen expression profile in humans differs significantly from rodents as COL6A3 does not appear to be the predominant collagen in adipose, muscle or liver. Our findings oppose those initially seen in rodent studies and most importantly, demonstrate a direct regulation of COL6A3 by leptin. This highlights the importance of a paracrine leptin signalling pathway in human AT and suggests an additional mechanism by which leptin can regulate ECM composition and with it AT expandability.

  • 9.
    Sauma, Lilian
    et al.
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Franck, Niclas
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences.
    Kjølhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Isolated primary human visceral fat cells release more angiotensin II than subcutaneous adipocytesManuscript (preprint) (Other academic)
    Abstract [en]

    Background. Visceral obesity relates strongly to the metabolic syndrome and hence to hypertension. Although a local renin-angiotensin-system (RAS) in fat tissue is known, very few studies have dealt with RAS in isolated primary human fat cells, in particular from the visceral compartment.

    Methods. Measurement of angiotensin II (Ang II) in medium from isolated primary human fat cells from visceral and subcutaneous adipose tissues and analyses of RAS-components in human fat cells and fat tissues.

    Results. Primary human fat cells from omental adipose tissue produced more Ang II than subcutaneous cells. Treatment with insulin did not affect Ang II production and body-massindex of the fat-donors was unrelated to Ang II production. The PPAR gamma agonist rosiglitazone inhibited Ang II production in both types of isolated fat cells while addition of the Ang II receptor antagonist eprosartan inhibited the production in only subcutaneous fat cells. Addition of 50 or 200 nM of Ang II inhibited the PPAR gamma response elementactivity (PPRE-activity) in visceral, but not in the subcutaneous adipocytes.

    Conclusions. Since high PPRE-activity induced by rosiglitazone inhibited the Ang II production, it is possible that reduced PPRE-activity in the visceral human fat cells, demonstrated by us earlier, can explain the comparatively high Ang II production in these cells. This could form the basis for a local paracrine viscous circle in visceral fat where low PPRE-activity increases Ang II production that is further enhanced by Ang II-mediated inhibition of PPRE-activity which ultimately leads to high concentrations of Ang II in human adipose tissue.

  • 10.
    Sauma, Lilian
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Franck, Niclas
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Paulsson, Johan F
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Westermark, Gunilla T.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Kjølhede, Preben
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Söderström, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Peroxisome proliferator activated receptor gamma activity is low in mature primary human visceral adipocytes2007In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 1, p. 195-201Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: The amount of visceral fat mass strongly relates to insulin resistance in humans. The transcription factor peroxisome proliferator activated receptor gamma (PPARG) is abundant in adipocytes and regulates genes of importance for insulin sensitivity. Our objective was to study PPARG activity in human visceral and subcutaneous adipocytes and to compare this with the most common model for human disease, the mouse.

    MATERIALS AND METHODS: We transfected primary human adipocytes with a plasmid encoding firefly luciferase controlled by PPARG response element (PPRE) from the acyl-CoA-oxidase gene and measured PPRE activity by emission of light. RESULTS: We found that PPRE activity was 6.6-fold higher (median) in adipocytes from subcutaneous than from omental fat from the same subjects (n = 23). The activity was also 6.2-fold higher in subcutaneous than in intra-abdominal fat cells when we used a PPARG ligand-binding domain-GAL4 fusion protein as reporter, demonstrating that the difference in PPRE activity was due to different levels of activity of the PPARG receptor in the two fat depots. Stimulation with 5 micromol/l rosiglitazone did not induce a PPRE activity in visceral adipocytes that was as high as basal levels in subcutaneous adipocytes. Interestingly, in mice of two different strains the PPRE activity was similar in visceral and subcutaneous fat cells.

    CONCLUSIONS/INTERPRETATION: We found considerably lower PPARG activity in visceral than in subcutaneous primary human adipocytes. Further studies of the molecular mechanisms behind this difference could lead to development of drugs that target the adverse effects of visceral obesity.

  • 11.
    Stenkula, Karin G.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Thorn, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Franck, Niclas
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences.
    Hallin, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Sauma, Lilian
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik H.
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences.
    Human, but not rat, IRS1 targets to the plasma membrane in both human and rat primary adipocytes2007In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 363, no 3, p. 840-845Article in journal (Refereed)
    Abstract [en]

    Adipocytes are primary targets for insulin control of metabolism. The activated insulin receptor phosphorylates insulin receptor substrate-1 (IRS1), which acts as a docking protein for downstream signal mediators. In the absence of insulin stimulation, IRS1 in rat adipocytes is intracellular but in human adipocytes IRS1 is constitutively targeted to the plasma membrane. Stimulation of adipocytes with insulin increased the amount of IRS1 at the plasma membrane 2-fold in human adipocytes, but >10-fold in rat adipocytes, with the same final amount of IRS1 at the plasma membrane in cells from both species. Cross-transfection of rat adipocytes with human IRS1, or human adipocytes with rat IRS1, demonstrated that the species difference was due to the IRS1 protein and not the cellular milieus or posttranslational modifications. Chimeric IRS1, consisting of the conserved N-terminus of rat IRS1 with the variable C-terminal of human IRS1, did not target the plasma membrane, indicating that subtle sequence differences direct human IRS1 to the plasma membrane.

  • 12.
    Strid, Tobias
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Svartz, Jesper
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Franck, Niclas
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Hallin, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Ingelsson, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Söderström, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Hammarström, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Distinct parts of leukotriene C-4 synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein2009In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 381, no 4, p. 518-522Article in journal (Refereed)
    Abstract [en]

    Leukotriene C-4 is a potent inflammatory mediator formed from arachidonic acid and glutathione. 5-Lipoxygenase (5-LO), 5-lipoxygenase activating protein (FLAP) and leukotriene C-4 synthase (LTC4S) participate in its biosynthesis. We report evidence that LTC4S interacts in vitro with both FLAP and 5-LO and that these interactions involve distinct parts of LTC4S. FLAP bound to the N-terminal part/first hydrophobic region of LTC4S. This part did not bind 5-LO which bound to the second hydrophilic loop of LTC4S. Fluorescent FLAP- and LTC4S-fusion proteins co-localized at the nuclear envelope. Furthermore, GFP-FLAP and GFP-LTC4S co-localized with a fluorescent ER marker. In testing HEK293/T or COS-7 cells GFP-5-LO was found mainly in the nuclear matrix. Upon stimulation with calcium ionophore, GFP-5-LO translocated to the nuclear envelope allowing it to interact with FLAP and LTC4S. Direct interaction of 5-LO and LTC4S in ionophore-stimulated (but not un-stimulated) cells was demonstrated by BRET using GFP-5-LO and Rluc-LTC4S.

  • 13.
    Svartz, Jesper
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Hallin, Elisabeth
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Franck, Niclas
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Strid, Tobias
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Söderström, Mats
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Studies of interactions between leukotriene C4 synthase, five-lipoxygenase activating protein and 5-lipoxygenaseManuscript (preprint) (Other academic)
    Abstract [en]

    Cysteinyl leukotrienes (cysLTs) are biologically active lipid mediators of great importance in asthma and inflammation. Three proteins are required to convert arachidonic acid into leukotriene C4 namely: five-lipoxygenase (5-LO), five-lipoxygenase activating protein (FLAP) and leukotriene C4 synthase (LTC4S). LTC4S and FLAP belong to the MAPEG (membrane associated proteins in eicosanoid and glutathione metabolism) family of proteins and are located on the nuclear envelope. Upon cell activation 5-LO translocates from the cytosol to the nuclear envelope enabling protein-protein interactions to occur between the three biosynthetic enzymes. GST pull-down experiments in this study demonstrate interaction between LTC4S and 5-LO, LTC4S and FLAP and between FLAP and 5-LO. Experiments with truncated mutants indicated that the second hydrophilic loop of LTC4S is important for interaction with 5-LO, and that the N-terminal part of LTC4S is important for FLAP interaction. Bioluminescence resonance energy transfer (BRET) experiments in transfected cells provided additional evidence that LTC4S interacts with 5-LO.

  • 14.
    Öst, Anita
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Svensson, Kristoffer
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Ruishalme, Iida
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Brännmark, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Franck, Niclas
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Krook, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Kjølhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics UHL.
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Attenuated mTOR signaling and enhanced autophagy in adipocytes from obese patients with type 2 diabetes2010In: Molecular medicine (Cambridge, Mass. Print), ISSN 1076-1551, E-ISSN 1528-3658, Vol. 16, no 07-Aug, p. 235-246Article in journal (Refereed)
    Abstract [en]

    The protein kinase mammalian target of rapamycin (mTOR) mediates insulin control ofprotein synthesis, autophagy, mitochondrial function, and, through feedback signaling tophosphorylation of IRS1 at serine residues, mTOR directly controls insulin signaling. Weshow that in adipocytes from patients with type 2 diabetes (T2D) insulin activation of mTORis attenuated and that the resultant phenotype is compatible with, and can be mimicked by,loss of mTOR activation. In T2D adipocytes mitochondrial function is impaired andautophagy strongly upregulated, with concomitant increased autophagic destruction ofmitochondria and lipofuscin particles, and a dependence on autophagy for ATP production.Conversely, mitochondrial dysfunction attenuates insulin activation of mTOR, enhancesautophagy and attenuates feedback to IRS1. Our findings put mTOR in the driver´s seat of aninsulin resistance that in adipocytes can be fuelled by mitochondrial dysfunction,inflammation, ER-stress, or hypoxia.

1 - 14 of 14
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf