Pleiotropic Effects of GIP on Islet Function Involve Osteopontin-Reference-Cited by-同舟云学术

Pleiotropic Effects of GIP on Islet Function Involve Osteopontin

Published:2011-08-20 Issue:9 Volume:60 Page:2424-2433
ISSN:0012-1797
Container-title:Diabetes
language:en
Short-container-title:

Author:

Lyssenko Valeriya¹,Eliasson Lena²,Kotova Olga³,Pilgaard Kasper⁴,Wierup Nils⁵,Salehi Albert⁶,Wendt Anna²,Jonsson Anna¹,De Marinis Yang Z.¹,Berglund Lisa M.³,Taneera Jalal¹,Balhuizen Alexander⁶,Hansson Ola¹,Osmark Peter¹,Dunér Pontus⁷,Brøns Charlotte⁴,Stančáková Alena⁸,Kuusisto Johanna⁸,Bugliani Marco⁹¹⁰,Saxena Richa¹¹¹²,Ahlqvist Emma¹,Kieffer Timothy J.¹³,Tuomi Tiinamaija¹⁴¹⁵,Isomaa Bo¹⁴¹⁶,Melander Olle¹⁷¹⁸,Sonestedt Emily¹⁹,Orho-Melander Marju¹⁹,Nilsson Peter²⁰,Bonetti Sara²¹,Bonadonna Riccardo²¹,Miccoli Roberto⁹,DelPrato Stefano⁹,Marchetti Piero⁹¹⁰,Madsbad Sten²²,Poulsen Pernille⁴,Vaag Allan⁴,Laakso Markku⁸,Gomez Maria F.⁷,Groop Leif¹

Affiliation:

1. Diabetes and Endocrinology, Department of Clinical Sciences, University Hospital Malmö, Lund University, Malmö, Sweden

2. Islet Cell Exocytosis, Department of Clinical Sciences, University Hospital Malmö, Lund University, Malmö, Sweden

3. Vascular ET-Coupling, Department of Clinical Sciences, University Hospital Malmö, Lund University, Malmö, Sweden

4. Steno Diabetes Center, Gentofte, Denmark

5. Neuroendocrine Cell Biology, Department of Experimental Medical Science, Lund University, Malmö, Sweden

6. Division of Endocrine Pharmacology, Department of Clinical Sciences, University Hospital Malmö, Lund University, Malmö, Sweden

7. Experimental Cardiovascular Research Unit, Department of Clinical Sciences, Lund University, University Hospital Malmö, Malmö, Sweden

8. Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland

9. Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy

10. Endocrinology and Metabolism of Organ and Cellular Transplantation, AOUP Pisa, Pisa, Italy

11. Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts

12. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts

13. Laboratory of Molecular and Cellular Medicine, Departments of Cellular and Physiological Sciences and Surgery, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada

14. Folkhalsan Research Centre, Helsinki, Finland

15. Department of Medicine, Helsinki University Central Hospital and Research Program of Molecular Medicine, University of Helsinki, Helsinki, Finland

16. The Department of Social Services and Health Care, Jakobstad, Finland

17. Center for Emergency Medicine, Malmö University Hospital, Malmö, Sweden

18. Hypertension and Cardiovascular Disease, Department of Clinical Sciences, Lund University, Clinical Research Centre, Malmö University Hospital, Malmö, Sweden

19. Diabetes and Cardiovascular Disease: Genetic Epidemiology, Department of Clinical Sciences, Lund University, Malmö, Sweden

20. Medicine, Department of Clinical Sciences, Lund University, University Hospital Malmö, Malmö, Sweden

21. Section of Endocrinology and Metabolism Diseases, Department of Medicine, University of Verona, Verona, Italy

22. Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark

Abstract

OBJECTIVE The incretin hormone GIP (glucose-dependent insulinotropic polypeptide) promotes pancreatic β-cell function by potentiating insulin secretion and β-cell proliferation. Recently, a combined analysis of several genome-wide association studies (Meta-analysis of Glucose and Insulin-Related Traits Consortium [MAGIC]) showed association to postprandial insulin at the GIP receptor (GIPR) locus. Here we explored mechanisms that could explain the protective effects of GIP on islet function. RESEARCH DESIGN AND METHODS Associations of GIPR rs10423928 with metabolic and anthropometric phenotypes in both nondiabetic (N = 53,730) and type 2 diabetic individuals (N = 2,731) were explored by combining data from 11 studies. Insulin secretion was measured both in vivo in nondiabetic subjects and in vitro in islets from cadaver donors. Insulin secretion was also measured in response to exogenous GIP. The in vitro measurements included protein and gene expression as well as measurements of β-cell viability and proliferation. RESULTS The A allele of GIPR rs10423928 was associated with impaired glucose- and GIP-stimulated insulin secretion and a decrease in BMI, lean body mass, and waist circumference. The decrease in BMI almost completely neutralized the effect of impaired insulin secretion on risk of type 2 diabetes. Expression of GIPR mRNA was decreased in human islets from carriers of the A allele or patients with type 2 diabetes. GIP stimulated osteopontin (OPN) mRNA and protein expression. OPN expression was lower in carriers of the A allele. Both GIP and OPN prevented cytokine-induced reduction in cell viability (apoptosis). In addition, OPN stimulated cell proliferation in insulin-secreting cells. CONCLUSIONS These findings support β-cell proliferative and antiapoptotic roles for GIP in addition to its action as an incretin hormone. Identification of a link between GIP and OPN may shed new light on the role of GIP in preservation of functional β-cell mass in humans.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

Link

https://journals.org/diabetes/diabetes/article-pdf/60/9/2424/402211/2424.pdf

Reference52 articles.

1. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels;Saxena;Science,2007

2. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis;Voight;Nat Genet,2010

3. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes;Zeggini;Nat Genet,2008

4. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge;Saxena;Nat Genet,2010

5. Human gastric inhibitory polypeptide receptor: cloning of the gene (GIPR) and cDNA;Yamada;Genomics,1995

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