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  • Lyssenko, ValeriyaLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups (author)

Pleiotropic Effects of GIP on Islet Function Involve Osteopontin

  • Article/chapterEnglish2011

Publisher, publication year, extent ...

  • 2011-08-20
  • American Diabetes Association,2011

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:e58b098d-f02d-497b-b1f5-e5c87f7c2fca
  • https://lup.lub.lu.se/record/2187102URI
  • https://doi.org/10.2337/db10-1532DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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Classification

  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • OBJECTIVE-The incretin hormone GIP (glucose-dependent insulinotropic polypeptide) promotes pancreatic beta-cell function by potentiating insulin secretion and beta-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 beta-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 beta-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 beta-cell mass in humans. Diabetes 60:2424-2433, 2011

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Eliasson, LenaLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Diabetes - Islet Cell Exocytosis,Lund University Research Groups(Swepub:lu)mphy-lel (author)
  • Kotova, OlgaLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups(Swepub:lu)med-oak (author)
  • Pilgaard, Kasper (author)
  • Wierup, NilsLund University,Lunds universitet,Neuroendokrin cellbiologi,Forskargrupper vid Lunds universitet,Neuroendocrine Cell Biology,Lund University Research Groups(Swepub:lu)mphy-nwi (author)
  • Salehi, S AlbertLund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)farm-sal (author)
  • Wendt, AnnaLund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups(Swepub:lu)mphy-awe (author)
  • Jonsson, AnnaLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)med-jsa (author)
  • De Marinis, Yang Z.Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)wbl-yzh (author)
  • Berglund, LisaLund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Vascular Physiology,Lund University Research Groups,Cardiovascular Research - Immunity and Atherosclerosis(Swepub:lu)mphy-lni (author)
  • Taneera, JalalLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)stem-jta (author)
  • Balhuizen, AlexanderLund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)med-abn (author)
  • Hansson, OlaLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)medk-oha (author)
  • Osmark, PeterLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)medk-pos (author)
  • Dunér, PontusLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups(Swepub:lu)medf-pdu (author)
  • Brons, Charlotte (author)
  • Stancakova, Alena (author)
  • Kuusisto, Johanna (author)
  • Bugliani, Marco (author)
  • Saxena, Richa (author)
  • Ahlqvist, EmmaLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)infl-eah (author)
  • Kieffer, Timothy J. (author)
  • Tuomi, Tiinamaija (author)
  • Isomaa, Bo (author)
  • Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups(Swepub:lu)endo-ome (author)
  • Sonestedt, EmilyLund University,Lunds universitet,Nutritionsepidemiologi,Forskargrupper vid Lunds universitet,Nutrition Epidemiology,Lund University Research Groups(Swepub:lu)medf-eso (author)
  • Orho-Melander, MarjuLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-mor (author)
  • Nilsson, PeterLund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups(Swepub:lu)medf-pni (author)
  • Bonetti, Sara (author)
  • Bonadonna, Riccardo (author)
  • Miccoli, Roberto (author)
  • DelPrato, Stefano (author)
  • Marchetti, Piero (author)
  • Madsbad, Sten (author)
  • Poulsen, Pernille (author)
  • Vaag, Allan (author)
  • Laakso, Markku (author)
  • Gomez, MariaLund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Vascular Physiology,Lund University Research Groups,Cardiovascular Research - Immunity and Atherosclerosis(Swepub:lu)mphy-mgo (author)
  • Groop, LeifLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-lgr (author)
  • Genomik, diabetes och endokrinologiForskargrupper vid Lunds universitet (creator_code:org_t)

Related titles

  • In:Diabetes: American Diabetes Association60:9, s. 2424-24331939-327X0012-1797

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