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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.

Jonsson, Anna LU ; Ladenvall, Claes LU ; Ahluwalia, Tarunveer Singh; Kravic, Jasmina LU ; Krus, Ulrika LU ; Taneera, Jalal LU ; Isomaa, Bo; Tuomi, Tiinamaija LU ; Renström, Erik LU and Groop, Leif LU , et al. (2013) In Diabetes 62(8). p.2978-2983
Abstract
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,... (More)
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. (Less)
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type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
62
issue
8
pages
2978 - 2983
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000322431100044
  • pmid:23557703
  • scopus:84891722250
ISSN
1939-327X
DOI
10.2337/db12-1627
language
English
LU publication?
yes
id
d886668d-06ba-486d-9181-f537342112b5 (old id 3734131)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23557703?dopt=Abstract
date added to LUP
2013-05-02 15:38:26
date last changed
2019-03-27 01:22:19
@article{d886668d-06ba-486d-9181-f537342112b5,
  abstract     = {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.},
  author       = {Jonsson, Anna and Ladenvall, Claes and Ahluwalia, Tarunveer Singh and Kravic, Jasmina and Krus, Ulrika and Taneera, Jalal and Isomaa, Bo and Tuomi, Tiinamaija and Renström, Erik and Groop, Leif and Lyssenko, Valeriya},
  issn         = {1939-327X},
  language     = {eng},
  number       = {8},
  pages        = {2978--2983},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Effect of Common Genetic Variants Associated with Type 2 Diabetes and Glycemic Traits on α- and β-cell Function and Insulin Action in Man.},
  url          = {http://dx.doi.org/10.2337/db12-1627},
  volume       = {62},
  year         = {2013},
}