liu.seSearch for publications in DiVA
Change search
Link to record
Permanent link

Direct link
BETA
Bäck, Karolina
Publications (7 of 7) Show all publications
Bäck, K., Islam, R., Johansson, G., Chisalita, I. S. & Arnqvist, H. (2012). Insulin and IGF1 receptors in human cardiac microvascular endothelial cells: metabolic, mitogenic and anti-inflammatory effects. Journal of Endocrinology, 215(1), 89-96
Open this publication in new window or tab >>Insulin and IGF1 receptors in human cardiac microvascular endothelial cells: metabolic, mitogenic and anti-inflammatory effects
Show others...
2012 (English)In: Journal of Endocrinology, ISSN 0022-0795, E-ISSN 1479-6805, Vol. 215, no 1, p. 89-96Article in journal (Refereed) Published
Abstract [en]

Diabetes is associated with microcirculatory dysfunction and heart failure and changes in insulin and IGF1 levels. Whether human cardiac microvascular endothelial cells (HMVEC-Cs) are sensitive to insulin and/or IGF1 is not known. We studied the role of insulin receptors (IRs) and IGF1 receptors (IGF1Rs) in metabolic, mitogenic and anti-inflammatory responses to insulin and IGF1 in HMVEC-Cs and human umbilical vein endothelial cells (HUVECs). IR and IGF1R gene expression was studied using real-time RT-PCR. Receptor protein expression and phosphorylation were determined by western blot and ELISA. Metabolic and mitogenic effects were measured as glucose accumulation and thymidine incorporation. An E-selectin ELISA was used to investigate inflammatory responses. According to gene expression and protein in HMVEC-Cs and HUVECs, IGF1R is more abundant than IR. Immunoprecipitation with anti-IGF1R antibody and immunoblotting with anti-IR antibody and vice versa, showed insulin/IGF1 hybrid receptors in HMVEC-Cs. IGF1 at a concentration of 10(-8) mol/l significantly stimulated phosphorylation of both IGF1R and IR in HMVEC-Cs. In HUVECs IGF1 10(-8) mol/l phosphorylated IGF1R. IGF1 stimulated DNA synthesis at 10(-8) mol/l and glucose accumulation at 10(-7) mol/l in HMVEC-Cs. TNF-alpha dramatically increased E-selectin expression, but no inflammatory or anti-inflammatory effects of insulin, IGF1 or high glucose were seen. We conclude that HMVEC-Cs express more IGF1Rs than IRs, and mainly react to IGF1 due to the predominance of IGF1Rs and insulin/IGF1 hybrid receptors. TNF-alpha has a pronounced pro-inflammatory effect in HMVEC-Cs, which is not counteracted by insulin or IGF1.

Place, publisher, year, edition, pages
Society for Endocrinology, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-86558 (URN)10.1530/JOE-12-0261 (DOI)000309000000010 ()
Available from: 2012-12-19 Created: 2012-12-19 Last updated: 2017-12-06
Bäck, K., Brännmark, C., Strålfors, P. & Arnqvist, H. (2011). Differential effects of IGF-I, IGF-II and insulin in human preadipocytes and adipocytes - Role of insulin and IGF-I receptors. Molecular and Cellular Endocrinology, 339(02-jan), 130-135
Open this publication in new window or tab >>Differential effects of IGF-I, IGF-II and insulin in human preadipocytes and adipocytes - Role of insulin and IGF-I receptors
2011 (English)In: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 339, no 02-jan, p. 130-135Article in journal (Refereed) Published
Abstract [en]

We compared insulin and IGF effects in adipocytes expressing IR (insulin receptors), and preadipocytes expressing IR and IGF-IR (IGF-I receptors). Treatment of adipocytes with insulin, IGF-II or IGF-I resulted in phosphorylation of IR. Order of potency was insulin greater thanIGF-IIgreater than IGF-I. In preadipocytes IR, IGF-IR and insulin/IGF-I hybrid receptors (HR) were detected. Treatment of preadipocytes with IGF-I and IGF-II 10(-8) M resulted in activation of IGF-IR and IR whereas insulin was more potent in activating IR, with no effect on IGF-IR. In adipocytes glucose transport was 100-fold more sensitive to insulin than to IGFs and the maximal effect was higher with insulin. In preadipocytes glucose accumulation and DNA synthesis was equally sensitive to insulin and IGFs but the maximal effect was higher with IGF-I. In conclusion, insulin and IGF-I activate their cognate receptors and IGF-I also HR. IGF-II activates IR, IGF-IR and HR. Insulin and IGF-I are partial agonists to each others receptors.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam., 2011
Keywords
Growth factors; Hybrid receptors; Receptor activation; DNA synthesis; Glucose metabolism
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69862 (URN)10.1016/j.mce.2011.04.005 (DOI)000292580100016 ()
Available from: 2011-08-10 Created: 2011-08-08 Last updated: 2017-12-08
Bäck, K. (2011). Interaction between insulin and IGF-I receptors in insulin sensitive and insulin resistant cells and tissues. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Interaction between insulin and IGF-I receptors in insulin sensitive and insulin resistant cells and tissues
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Insulin and insulin-like growth factor I (IGF-I) are two related peptides with similar structure. They mediate their effects by binding to their respective receptor, the insulin receptor (IR) and the IGF-I receptor (IGF-IR) and induce intracellular signalling cascades resulting in metabolic or mitogenic effects. The relative abundance of IR and IGF-IR is of importance for the type of effect that is the outcome of the signal. There are few studies investigating the relative receptor abundance and its effects in human cells and tissues.

In this thesis we wanted to study abundance and regulation of insulin and IGF-I receptors in different human cells and tissues and examine the effects of variations in insulin and IGF-I receptor abundance between different cells and tissues.

We examined IR and IGF-IR gene and protein expression and the effects of insulin and IGF-I on receptor phosphorylation, DNA synthesis and glucose transport.

Our results show that there is a large variation in the distribution of IR and IGF-IR in different human cells and tissues. Renal artery intima-media expressed predominantly IGF-IR while in liver IR was the predominant receptor type.

Differentiation of human preadipocytes results in a change in relative expression of IGF-IR to IR. Mature adipocytes express almost 10-fold more IR than IGF-IR while preadipocytes express almost the same amounts of both receptors. Mature tissues, such as liver, skeletal muscle, myometrium and renal artery intima-media, express predominantly IR-B. Preadipocytes express IR-A and the expression of IR-B is induced during differentiation.

We could show the presence of insulin/IGF-I hybrid receptors in preadipocytes but not in mature adipocytes. Cultured endothelial cells express mostly IGF-IR and insulin/IGF-I hybrid receptors and these cells respond mainly to IGF-I. Due to the large abundance of IR mature adipocytes are sensitive to insulin but insensitive to IGF-I whereas preadipocytes expressing equal amounts of both receptors respond to both insulin and IGF-I. Insulin and IGF-I are only partial agonists to each other’s receptors in human preadipocytes and adipocytes.

The overall results indicate that differential expression of IGF-IR and IR is a key mechanism in regulation of growth and metabolism.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. p. 46
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1268
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71892 (URN)978-91-7393-042-0 (ISBN)
Public defence
2011-12-09, Berzeliussalen, hus 463, ingång 65, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2011-11-09 Created: 2011-11-09 Last updated: 2011-11-09Bibliographically approved
Bäck, K. & Arnqvist, H. (2009). Changes in insulin and IGF-I receptor expression during differentiation of human preadipocytes. Growth Hormone & IGF Research, 19(2), 101-111
Open this publication in new window or tab >>Changes in insulin and IGF-I receptor expression during differentiation of human preadipocytes
2009 (English)In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 19, no 2, p. 101-111Article in journal (Refereed) Published
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.

Keywords
Insulin receptor isoforms, Cell metabolism, Growth factors
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17895 (URN)10.1016/j.ghir.2008.06.004 (DOI)
Note
Original Publication: Karolina Bäck and Hans Arnqvist, Changes in insulin and IGF-I receptor expression during differentiation of human preadipocytes, 2009, GROWTH HORMONE and IGF RESEARCH, (19), 2, 101-111. http://dx.doi.org/10.1016/j.ghir.2008.06.004 Copyright: Elsevier Science B.V., Amsterdam http://www.elsevier.com/ Available from: 2009-05-20 Created: 2009-04-24 Last updated: 2017-12-13Bibliographically approved
Chisalita, I. S., Johansson, G., Liefvendahl, E., Bäck, K. & Arnqvist, H. (2009). Human aortic smooth muscle cells are insulin resistant at the receptor level but sensitive to IGF1 and IGF2. Journal of Molecular Endocrinology, 43(5-6), 231-239
Open this publication in new window or tab >>Human aortic smooth muscle cells are insulin resistant at the receptor level but sensitive to IGF1 and IGF2
Show others...
2009 (English)In: Journal of Molecular Endocrinology, ISSN 0952-5041, E-ISSN 1479-6813, Vol. 43, no 5-6, p. 231-239Article in journal (Refereed) Published
Abstract [en]

Whether insulin, in physiological concentrations, has direct effects on vascular smooth muscle cells (VSMC) remains controversial. Our aim was to characterize the mechanism for insulin resistance in VSMCs. For comparison, effects of insulin-like growth factor (IGF)-I and IGF-II were also studied. Cultured human aortic smooth muscle cells (HASMC) were used. Receptor mRNA was analysed by quantitative RT-PCR and receptor protein by ELISA and Western Blot. The biological effects were studied by thymidine incorporation and glucose accumulation.

In HASMC both mRNA and protein expression of IGF-I receptors (IGF-IR) were 5 fold higher compared to insulin receptor (IR). IR isoform A mRNA was 13 times more expressed than IR isoform B. Immunoprecipitation and Western blot showed co precipitation of IR and IGF-IR indicating the presence of hybrid IR/IGF-IR.

Phosphorylation of the IGF-IR β-subunit was obtained by IGF-I 10-9-10-8mol l-1 and IGF-II 10-8mol l-1. IR β-subunit was phosphorylated by IGF-I 10-8mol l-1 but not by insulin. IGF-I stimulated IRS-I at 10-8mol l-1, Akt and Erk 1/2 at 10-9-10-8mol l-1, respectively. IGF-II stimulated Akt at 10-8mol l-1 whereas insulin had no effect. IGF-I and IGF-II at a concentration of 10-8-10-7mol l-1 significantly stimulated 3H-thymidine incorporation, whereas insulin did not. 14C-Glucose accumulation was stimulated by IGF-I or IGF-II 10-8-10-7mol l-1, and also by insulin 10-7mol l-1.

Our results suggest that IGF-IR and hybrid IR/IGF-IR are activated by physiological concentrations of IGF-I and IGF-II in HASMC and this causes downstream signaling and biological effects, while insulin has no effect on its receptor or downstream signaling probably due to a preponderance of IGF-IR and incorporation of IR into hybrid IR/IGF-IR.

Keywords
Receptors, insulin, IGF-I, IGF-II, IRS-1, Erk 1/2, Akt, DNA-synthesis, glucose accumulation.
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-19283 (URN)10.1677/JME-09-0021 (DOI)
Available from: 2009-06-16 Created: 2009-06-16 Last updated: 2017-12-13Bibliographically approved
Bäck, K., Wahlström, O., Kjölhede, P., Sandström, P., Gasslander, T. & Arnqvist, H.Differential expression of insulin and IGF-I receptors in human tissues.
Open this publication in new window or tab >>Differential expression of insulin and IGF-I receptors in human tissues
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Insulin and IGF-I are related peptides with similar structure. They both signal via their cognate receptors, the insulin receptor (IR) and the insulin-like growth factor (IGF)-I receptor (IGF-IR).

Our aim was to simultaneously measure the amount of insulin and IGF-I receptors in different human tissues and also the IR-A and IR-B isoforms to study tissue specific expression

Renal artery intima-media, myometrium, skeletal muscle or liver tissue samples were obtained from patients undergoing surgery. IR, IGF-IR, IR-A and IR-B gene expression was investigated with real-time RT-PCR and expression of IR and IGF-IR protein was examined by Western blot and ELISA.

Renal arteries and myometrium expressed the IGF-IR gene to a higher extent than the IR gene, liver expressed more IR than IGF-IR and skeletal muscle expressed almost equal amounts of both receptors. IR-B was the most abundant isoform in all tissues. With Western blot we could detect IR in skeletal muscle, liver and myometrium. With ELISA we found that, normalized to total protein, the highest levels of IGF-IR were found in renal arteries and myometrium and low levels in skeletal muscle and liver. The highest levels of IR were found in liver.

In conclusion there is a large variation in the quantity and ratio of insulin receptors and IGF-I receptors expressed in different tissues, the extremes being arterial intima media with predominantly IGF-I receptors and liver with predominantly insulin receptors. This suggests that differential expression of insulin and IGF-I receptors is a key mechanism in regulation of growth and metabolism.

Keywords
liver, skeletal muscle, myometrium, renal artery intima-media
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71891 (URN)
Available from: 2011-11-09 Created: 2011-11-09 Last updated: 2019-06-28Bibliographically approved
Bäck, K., Islam, R., Johansson, G., Chisalita, S. & Arnqvist, H.Role of insulin and IGF-I receptors in human cardiac microvascular endothelial cells; metabolic, mitogenic and anti-inflammatory effects.
Open this publication in new window or tab >>Role of insulin and IGF-I receptors in human cardiac microvascular endothelial cells; metabolic, mitogenic and anti-inflammatory effects
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Diabetes is associated with coronary microcirculatory dysfunction and heart failure as well as changes in insulin and IGF-I levels. Our aim was to study the role of insulin receptors and IGF-I receptors in metabolic, mitogenic and anti-inflammatory responses to insulin and IGF-I in human cardiac microvascular endothelial cells (HMVEC-C) and, for comparison, also human umbilical vein endothelial cells (HUVEC). Insulin receptor (IR) and IGF-I receptor (IGF-IR) gene expression was studied with real-time RT-PCR. Receptor protein expression and phosphorylation was determined with Western blot and ELISA. The metabolic and mitogenic effects were measured as glucose accumulation and thymidine incorporation. An E-selectin ELISA was used to investigate the anti-inflammatory responses. IGF-IR was more abundant than IR both regarding gene expression and protein in HMVEC-C and HUVEC. Immunoprecipitation with anti-IGF-IR antibody and immunoblotting with anti-IR antibody and vice versa, showed insulin/IGF-I hybrid receptors in these cells. IGF-I 10-8 M significantly stimulated phosphorylation of both IGF-IR and IR in HMVEC-C. In HUVEC IGF-I 10-8 M phosphorylated IGF-IR. IGF-I also stimulated DNA synthesis at 10-8 M and glucose accumulation at 10-7 M. TNF-α significantly increased E-selectin expression whereas no effects were found by insulin, IGF-I or high glucose.

We conclude that HMVEC-C express more IGF-I receptors than insulin receptors and at physiological concentrations of insulin and IGF-I mainly reacts to IGF-I probably due to the predominance of IGF-I receptors and insulin/IGF-I hybrid receptors. TNF-α has a pronounced pro-inflammatory effect in HMVEC-C which is not counteracted by insulin or IGF-I.

Keywords
receptor ELISA, thymidine incorporation, glucose accumulation, E-selectin expression
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71890 (URN)
Available from: 2011-11-09 Created: 2011-11-09 Last updated: 2011-11-09Bibliographically approved
Organisations

Search in DiVA

Show all publications