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Differential expression of insulin and IGF-I receptors in human tissues
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. (Hans Arnqvist)
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
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.
Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
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(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.

Keyword [en]
liver, skeletal muscle, myometrium, renal artery intima-media
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-71891OAI: oai:DiVA.org:liu-71891DiVA: diva2:455203
Available from: 2011-11-09 Created: 2011-11-09 Last updated: 2011-11-09Bibliographically 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, KarolinaWahlström, OlaKjölhede, PrebenSandström, PerGasslander, ThomasArnqvist, Hans

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Bäck, KarolinaWahlström, OlaKjölhede, PrebenSandström, PerGasslander, ThomasArnqvist, Hans
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Cell BiologyFaculty of Health SciencesOrthopaedics and Sports MedicineDepartment of Orthopaedics in LinköpingObstetrics and gynecologyDepartment of Gynecology and Obstetrics in LinköpingSurgeryDepartment of Surgery in ÖstergötlandDepartment of Endocrinology and Gastroenterology UHL
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