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Changes in insulin and IGF-I receptor expression during differentiation of human preadipocytes
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, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
2009 (English)In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 19, no 2, 101-111 p.Article 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.

Place, publisher, year, edition, pages
2009. Vol. 19, no 2, 101-111 p.
Keyword [en]
Insulin receptor isoforms, Cell metabolism, Growth factors
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-17895DOI: 10.1016/j.ghir.2008.06.004OAI: oai:DiVA.org:liu-17895DiVA: diva2:212984
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
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, KarolinaArnqvist, Hans

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Cell BiologyFaculty of Health SciencesDepartment of Endocrinology and Gastroenterology UHL
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