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

Anna Jonsson; Claes Ladenvall; Tarun Veer Singh Ahluwalia; Jasmina Kravic; Ulrika Krus; Jalal Taneera; B. Isomaa; T. Tuomi; F. Renström; L. Groop; Valeriya Lyssenko

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

Anna Jonsson, Claes Ladenvall, Tarun Veer Singh Ahluwalia, Jasmina Kravic, Ulrika Krus, Jalal Taneera, B. Isomaa, T. Tuomi, F. Renström, L. Groop, Valeriya Lyssenko

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 a-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.

Original language	English
Journal	Diabetes, The American Diabetes Association
Volume	62
Issue number	8
Publication status	Published - 4 Apr 2013

Keywords

Faculty of Health and Medical Sciences

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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http://www.ncbi.nlm.nih.gov/pubmed/23557703

Cite this

Jonsson, A., Ladenvall, C., Ahluwalia, T. V. S., Kravic, J., Krus, U., Taneera, J., Isomaa, B., Tuomi, T., Renström, F., Groop, L., & Lyssenko, V. (2013). Effect of Common Genetic Variants Associated with Type 2 Diabetes and Glycemic Traits on a- and ß-cell Function and Insulin Action in Man. Diabetes, The American Diabetes Association, 62(8). http://www.ncbi.nlm.nih.gov/pubmed/23557703

Effect of Common Genetic Variants Associated with Type 2 Diabetes and Glycemic Traits on a- and ß-cell Function and Insulin Action in Man. / Jonsson, Anna; Ladenvall, Claes; Ahluwalia, Tarun Veer Singh et al.

In: Diabetes, The American Diabetes Association, Vol. 62, No. 8, 04.04.2013.

Research output: Contribution to journal › Journal article › Research › peer-review

Jonsson, A, Ladenvall, C, Ahluwalia, TVS, Kravic, J, Krus, U, Taneera, J, Isomaa, B, Tuomi, T, Renström, F, Groop, L & Lyssenko, V 2013, 'Effect of Common Genetic Variants Associated with Type 2 Diabetes and Glycemic Traits on a- and ß-cell Function and Insulin Action in Man.', Diabetes, The American Diabetes Association, vol. 62, no. 8. <http://www.ncbi.nlm.nih.gov/pubmed/23557703>

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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 a-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.",

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AU - Ahluwalia, Tarun Veer Singh

AU - Kravic, Jasmina

AU - Krus, Ulrika

AU - Taneera, Jalal

AU - Isomaa, B.

AU - Tuomi, T.

AU - Renström, F.

AU - Groop, L.

AU - Lyssenko, Valeriya

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N2 - 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 a-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.

AB - 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 a-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.

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

Abstract

Keywords

UN SDGs

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Cite this