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Ulrika Krus

Coordinator

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Effect of Common Genetic Variants Associated with Type 2 Diabetes and Glycemic Traits on α- and β-cell Function and Insulin Action in Man.

Author

  • Anna Jonsson
  • Claes Ladenvall
  • Tarunveer Singh Ahluwalia
  • Jasmina Kravic
  • Ulrika Krus
  • Jalal Taneera
  • Bo Isomaa
  • Tiinamaija Tuomi
  • Erik Renström
  • Leif Groop
  • Valeriya Lyssenko

Summary, in English

Although meta-analyses of genome-wide association studies have identified more than 60 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes and/or glycemic traits, there is little information whether these variants also affect α-cell function. The aim of the present study was to evaluate the effects of glycemia-associated genetic loci on islet function in vivo and in vitro. We studied 43 SNPs in 4,654 normoglycemic participants from the Finnish population-based PPP-Botnia study. Islet function was assessed, in vivo, by measuring insulin and glucagon concentrations during OGTT, and, in vitro, by measuring glucose stimulated insulin and glucagon secretion from human pancreatic islets. Carriers of risk variants in BCL11A, HHEX, ZBED3, HNF1A, IGF1 and NOTCH2 showed elevated, while those in CRY2, IGF2BP2, TSPAN8 and KCNJ11 decreased fasting and/or 2hr glucagon concentrations in vivo. Variants in BCL11A, TSPAN8, and NOTCH2 affected glucagon secretion both in vivo and in vitro. The MTNR1B variant was a clear outlier in the relationship analysis between insulin secretion and action, as well as between insulin, glucose and glucagon. Many of the genetic variants shown to be associated with type 2 diabetes or glycemic traits also exert pleiotropic in vivo and in vitro effects on islet function.

Department/s

  • Genomics, Diabetes and Endocrinology
  • Department of Clinical Sciences, Malmö
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2013

Language

English

Pages

2978-2983

Publication/Series

Diabetes

Volume

62

Issue

8

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1939-327X