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Differential effects of IGF-I, IGF-II and insulin in human preadipocytes and adipocytes - Role of insulin and IGF-I receptors
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
2011 (English)In: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 339, no 02-jan, 130-135 p.Article 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. Vol. 339, no 02-jan, 130-135 p.
Keyword [en]
Growth factors; Hybrid receptors; Receptor activation; DNA synthesis; Glucose metabolism
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-69862DOI: 10.1016/j.mce.2011.04.005ISI: 000292580100016OAI: oai:DiVA.org:liu-69862DiVA: diva2:433422
Available from: 2011-08-10 Created: 2011-08-08 Last updated: 2017-12-08
In thesis
1. Interaction between insulin and IGF-I receptors in insulin sensitive and insulin resistant cells and tissues
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. 46 p.
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

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Bäck, KarolinaBrännmark, CeciliaStrålfors, PeterArnqvist, Hans

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