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  • 1.
    Bäck, Karolina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Changes in insulin and IGF-I receptor expression during differentiation of human preadipocytes2009In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 19, no 2, p. 101-111Article in journal (Refereed)
    Abstract [en]

    Mature adipocytes originate from fibroblast-like precursor cells, preadipocytes, which differentiate to obtain the characteristics of adipocytes. Our aim was to investigate how differentiation of human preadipocytes affects the distribution of insulin receptors (IR) and IGF-I receptors (IGF-IR) and other cell characteristics. Preadipocytes were differentiated using indomethacine, dexamethasone, isobutyl-methylxantine (IBMX) and high concentration of insulin. Gene expression was quantified by real-time RT-PCT in preadipocytes (PA), differentiated preadipocytes (dPA) and mature adipocytes (mAD). The amount of expressed receptor protein was analyzed using receptor specific ELISAs and Western blot. We also studied DNA synthesis with radiolabeled thymidine incorporation and glucose accumulation with radiolabeled glucose. Differentiation of PA increased gene expression of IR but not IGF-IR, GLUT4, growth hormone receptor (GHR) and adiponectin appeared or increased. In PA and dPA only IR-A was expressed whereas also IR-B was detected in mAD. By Western blot and ELISA, IR and IGF-IR was phosphorylated by their own ligant at 1 nM and in dPA the acitivation of both receptors was stimulated by IGF-I, but not insulin, at 1 nM. Accumulation of glucose in PA was increased by insulin at 10 nM and by IGF-I at 1 nM and 10 nM. DNA synthesis was increased by insulin and IGF-I at 10 nM.

    In conclusion, both IR and IGF-IR are present in human preadipocytes and adipocytes. Differentiation is characterized by an increased IR/IGF-IR ratio.

  • 2.
    Chisalita, Simona I.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Dekker Nitert, Marloes
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans J.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Characterisation of receptors for IGF-I and insulin: evidence for hybrid insulin/IGF-I receptor in human coronary artery endothelial cells2006In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 16, no 4, p. 258-266Article in journal (Refereed)
    Abstract [en]

    Objective: Coronary artery disease is a prevalent cause of morbidity and mortality in diabetes. Little is known about insulin-like growth factor-I receptors (IGF-IR) and insulin receptors (IR) in human coronary endothelium. Our aim was to characterize IGF-IR and IR in human coronary artery endothelial cells (HCAEC).

    Design: Cultured human coronary artery endothelial cells were used. Gene expression was measured by quantitative real-time RTPCR analysis and receptor affinity by ligand binding. Receptor protein, phosphorylation of IGF-IR and IR b-subunit as well as the presence of hybrid insulin receptor/Insulin-like growth factor-I receptor (Hybrid IR/IGF-IR) was analyzed by immunoprecipitation and Western blot. Postreceptor effects of insulin and IGF-I were assed by 3H-thymidine incorporation.

    Results: The gene expression of IGF-IR was several folds higher than that of IR. and insulin receptor isoform A (IR-A) was 20-fold more expressed than insulin receptor isoform B (IR-B) in HCAEC. The specific binding of 125I-IGF-I was higher than that of 125Iinsulin. Insulin and the new long acting insulin analog, glargine, interacted with the IGF-IR with over thousand and 100-fold less potency than IGF-I itself, whereas IGF-II had 6 times lower potency than IGF-I. Phosphorylation of the IGF-IR b-subunit was obtained by concentrations of 10-10–10-8 M IGF-I, 10-6 M of insulin, inconsistently by 10-8 M insulin and not at all by 10-10–10-9 M insulin. The IR b-subunit was phosphorylated by insulin and IGF-I at concentrations of 10-9–10-8 M. When immunoprecipitating with specific monoclonal anti-IR or anti-IGF-IR a-subunit antibodies we found bands situated in slightly different positions suggesting the presence of Hybrid IR/IGF-IR. IGF-I, IGF-II and insulin (10-9–10-7 M) had no significant effect on 3H-thymidine incorporation into DNA.

    Conclusions: Human coronary endothelial cells express more IGF-IR than IR, mainly IR-A, and also Hybrid IR/IGF-IR. Both IGF-I and insulin phosphorylate their receptors, but only IGF-I seems to phosphorylate Hybrid IR/IGF-IR. Our study provides experimental evidence for a possible role of IGF-IR, IR and Hybrid IR/IGF-IR in human coronary artery endothelial cells.

  • 3.
    Grant, P.A.
    et al.
    Department of Obstetrics/Gynaecology, University of Adelaide, Adelaide, SA 5005, Australia.
    Kind, K.L.
    Department of Obstetrics/Gynaecology, University of Adelaide, Adelaide, SA 5005, Australia.
    Roberts, C.T.
    Department of Obstetrics/Gynaecology, University of Adelaide, Adelaide, SA 5005, Australia.
    Sohlström, A.
    Linköping University, Department of Biomedicine and Surgery, Nutrition. Linköping University, Faculty of Health Sciences.
    Owens, P.C.
    Department of Obstetrics/Gynaecology, University of Adelaide, Adelaide, SA 5005, Australia.
    Owens, J.A.
    Department of Obstetrics/Gynaecology, University of Adelaide, Adelaide, SA 5005, Australia.
    Late pregnancy increases hepatic expression of insulin-like growth factor-I in well nourished guinea pigs2005In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 15, no 2, p. 165-171Article in journal (Refereed)
    Abstract [en]

    Blood IGF-I concentrations are persistently elevated throughout pregnancy in humans and guinea pigs and may regulate substrate partitioning between mother and conceptus. In the guinea pig, liver and adipose tissue have recently been suggested to contribute to the increased levels of circulating IGF-I in mid-pregnancy, but whether this persists in late pregnancy in undernutrition is not known. Therefore the effect of pregnancy and undernutrition on circulating IGF-I and hepatic expression of IGF-I in late gestation in the guinea pig was examined. Female guinea pigs (Cavia porcellus) were fed ad libitum throughout pregnancy or 70% of ad libitum intake for 28 days prior to and throughout pregnancy (term is 69 d). Non-pregnant animals were maintained for 88 days on the same diets. Plasma IGF-I was measured by RIA after molecular sieving chromatography at low pH. Abundances of IGF-I and ß-actin mRNA in maternal liver were quantified by digoxigenin-ELISA after RT PCR. Late pregnancy increased both the concentration of IGF-I protein (p < 0.001) in plasma and the relative abundance of liver IGF-I mRNA (p < 0.001) in ad libitum fed, but not in feed restricted pregnant guinea pigs. The concentration of IGF-I protein in plasma correlated positively with the relative abundance of IGF-I mRNA in liver overall (p < 0.002), suggesting the liver as a major source of endocrine IGF-I in late pregnant guinea pigs. This study demonstrates that hepatic expression of IGF-I remains elevated during late pregnancy in the well fed guinea pig, which is in contrast to that observed in other non-human species. © 2005 Elsevier Ltd. All rights reserved.

  • 4.
    Hedman, Christina
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Frystyk, Jan
    Medical Research Laboratories, Clinical Institute and Medical Department, Aarhus University Hospital, Aarhus, Denmark.
    Fridell, Karin
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Jönsson, Anna
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Flyvbjerg, Allan
    Medical Research Laboratories, Clinical Institute and Medical Department, Aarhus University Hospital, Aarhus, Denmark.
    Lindström, Torbjörn
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    The IGF-system is not affected by a twofold change in protein intake in patients with type 1 diabetes2005In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 15, no 4, p. 304-310Article in journal (Refereed)
    Abstract [en]

    Objective In type 1 diabetes the circulating IGF-system is altered with low IGF-I and changes in levels of IGF-binding proteins (IGFBPs) which may be of importance for the development of diabetes complications. Our aim was to study if IGF-I, as supported by experimental data in animals, can be affected by dietary protein intake.

    Design and methods Twelve patients with type 1 diabetes, age 37.5 ± 10.0 years (mean ± SD), diabetes duration 20.1 ± 9.3 years and HbA1c 6.3 ± 0.6% were allocated to isocaloric diets with either low normal protein content (LNP), (10 E%; 0.9 g protein/kg body weight) or high normal protein content (HNP) (20 E%; 1.8 g protein/kg body weight) in an open randomised cross-over study. Each diet was taken for 10 days with a wash-out period of 11 days in between. Circulating levels of total and free IGF-I and -II, IGFBP-1, -2 and -3 and GH-binding protein (GHBP) as well as ghrelin were measured with validated in-house immunoassays.

    Results At day 10, urinary urea excretion was 320 ± 75 mmol/24 h during LNP diet compared with 654 ± 159 mmol/24 h during HNP diet (p < 0.001). There were no changes in body weight or glycaemic control between the diets. Fasting levels of total IGF-I were 121 ± 33 μg/L after LNP and 117 ± 28 μg/L after HNP diet (ns) and the corresponding concentrations of IGFBP-1 were 142(141) and 132(157) μg/L [median (IQR)] (ns). There were no differences in plasma concentrations of total IGF-II, free IGF-I and -II, IGFBP-3, GHBP and ghrelin, whereas a small difference was found for IGFBP-2 (302 ± 97 vs. 263 ± 66 μg/L; LNP vs. HNP; p < 0.04).

    Conclusions A twofold change of the dietary protein intake does not influence the altered circulating IGF-system in type 1 diabetes. In order to affect the IGF-system other interventions must be used.

  • 5.
    Sohlstrom, A
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden¤ Univ Adelaide, Dept Obstet & Gynaecol, Adelaide, SA 5005, Australia¤ Univ Adelaide, Dept Physiol, Adelaide, SA 5005, Australia.
    Fernberg, P
    Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden¤ Univ Adelaide, Dept Obstet & Gynaecol, Adelaide, SA 5005, Australia¤ Univ Adelaide, Dept Physiol, Adelaide, SA 5005, Australia.
    Owens, JA
    Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden¤ Univ Adelaide, Dept Obstet & Gynaecol, Adelaide, SA 5005, Australia¤ Univ Adelaide, Dept Physiol, Adelaide, SA 5005, Australia.
    Owens, PC
    Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden¤ Univ Adelaide, Dept Obstet & Gynaecol, Adelaide, SA 5005, Australia¤ Univ Adelaide, Dept Physiol, Adelaide, SA 5005, Australia.
    Maternal nutrition affects the ability of treatment with IGF-I and IGF-II to increase growth of the placenta and fetus, in guinea pigs2001In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 11, no 6, p. 392-398Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate how administration of IGF-I and IGF-II, during early to mid pregnancy, affects maternal growth and body composition as well as fetal and placental growth, in ad libitum fed, and in moderately, chronically food restricted guinea pigs. From day 20 of gestation, mothers (3-4 months old) were infused with IGF-I, IGF-II (565 mug/day) or vehicle for 17 days and then killed on day 40 of gestation. Maternal organ weights, fetal and placental weights were assessed. Treatment with IGFs did not alter body weight gain and had small effects on body composition in the mothers. Both IGF-I and IGF-II increased fetal and placental weights in ad libitum fed dams and IGF-I increased placental weight in food restricted dams. In conclusion, treatment with IGF-I during the first half of pregnancy stimulates placental growth in both ad libitum fed and food restricted guinea pigs without affecting maternal growth while fetal growth is stimulated by IGF treatment only in ad libitum fed animals. (C) 2001 Elsevier Science Ltd.

  • 6.
    Van dijk, Peter R
    et al.
    Isala, Diabetes Centre, Zwolle, The Netherlands.
    Logtenberg, Susan J J
    University Medical Center Groningen, The Netherlands.
    Chisalita, Ioana Simona
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Hedman, Christina A.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Groenier, Klaas H
    University Medical Center Groningen, The Netherlands.
    Gans, Reinold O B
    University Medical Center Groningen, The Netherlands.
    Kleefstra, Nanne
    University Medical Center Groningen, The Netherlands.
    Arnqvist, Hans J.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Bilo, Henk J G
    University Medical Center Groningen, The Netherlands.
    After 6years of intraperitoneal insulin administration IGF-I concentrations in T1DM patients are at low-normal level.2015In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 25, no 6, p. 316-319Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Low concentrations of insulin-like growth factor-I (IGFI) have been reported in type 1 diabetes mellitus (T1DM), suggested to be due to low insulin concentrations in the portal vein. The aim was to describe the long-term course of IGFI concentrations among T1DM subjects treated with continuous intraperitoneal (IP) insulin infusion (CIPII).

    DESIGN: Nineteen patients that participated in a randomized cross-over trial comparing CIPII and subcutaneous (SC) insulin therapy in 2006 were followed until 2012. IGF-I measurements were performed at the start of the 2006 study, after the 6month SC- and CIPII treatment phase in 2006 and during CIPII therapy in 2012. Z-scores were calculated to compare the IGF-I concentrations with age-specific normative range values of a non-DM reference population.

    RESULTS: In 2012, IGF-I Z-scores (-0.7; 95% confidence interval -1.3, -0.2) were significantly higher than at the start of the 2006 study (-2.5; -3.3, -1.8), the end of the SC (-2.0; -2.6, -1.5) and CIPII (-1.6; -2.1, -1.0) treatment phase with a mean difference of: 1.8 (0.9, 2.7), 1.3 (0.5, 2.1) and 0.8 (0.1, 1.6), respectively.

    CONCLUSION: After 6years of treatment with CIPII, IGF-I concentrations among T1DM patients increased to a level that is higher than during prior SC insulin treatment and is in the lower normal range compared to a non-DM reference population. The results of this study suggest that long-term IP insulin administration influences the IGF system in T1DM.

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