The T-allele of TCF7L2 rs7903146 associates with a reduced compensation of insulin secretion for insulin resistance induced by 9 days of bed rest

Amra C Alibegovic, Mette P Sonne, Lise Højbjerre, Torben Hansen, Oluf Pedersen, Gerrit van Hall, Jens J Holst, Bente Stallknecht, Flemming Dela, Allan Vaag

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2010-Apr
OriginalsprogEngelsk
TidsskriftDiabetes
Vol/bind59
Udgave nummer4
Sider (fra-til)836-43
Antal sider7
DOI
StatusUdgivet - 1. apr. 2010

Fingeraftryk

T Cell Transcription Factor 1
Insulin Resistance
Alleles
Insulin
Glucagon
Type 2 Diabetes Mellitus
Glucose Clamp Technique
R Factors
Glucose Tolerance Test
Fasting
Research Design
Liver

Citer dette

Alibegovic, Amra C ; Sonne, Mette P ; Højbjerre, Lise ; Hansen, Torben ; Pedersen, Oluf ; van Hall, Gerrit ; Holst, Jens J ; Stallknecht, Bente ; Dela, Flemming ; Vaag, Allan. / The T-allele of TCF7L2 rs7903146 associates with a reduced compensation of insulin secretion for insulin resistance induced by 9 days of bed rest. I: Diabetes. 2010 ; Bind 59, Nr. 4. s. 836-43.
@article{edae5b90a14011dfb242000ea68e967b,
title = "The T-allele of TCF7L2 rs7903146 associates with a reduced compensation of insulin secretion for insulin resistance induced by 9 days of bed rest",
abstract = "OBJECTIVE: The aim of this study was to determine whether the type 2 diabetes-associated T-allele of transcription factor 7-like 2 (TCF7L2) rs7903146 associates with impaired insulin secretion to compensate for insulin resistance induced by bed rest. RESEARCH DESIGN AND METHODS: A total of 38 healthy young Caucasian men were studied before and after bed rest using the hyperinsulinemic-euglycemic clamp technique combined with indirect calorimetry preceded by an intravenous glucose tolerance test. The TCF7L2 rs7903146 was genotyped using allelic discrimination performed with an ABI 7900 system. The genetic analyses were done assuming a dominant model of inheritance. RESULTS: The first-phase insulin response (FPIR) was significantly lower in carriers of the T-allele compared with carriers of the CC genotype before bed rest, with and without correction for insulin resistance. The incremental rise of FPIR in response to insulin resistance induced by bed rest was lower in carriers of the T-allele (P < 0.001). Fasting plasma glucagon levels were significantly lower in carriers of the T-allele before and after bed rest. While carriers of the CC genotype developed increased hepatic insulin resistance, the TCF7L2 rs7903146 did not influence peripheral insulin action or the rate of lipolysis before or after bed rest. CONCLUSIONS: Healthy carriers of the T-allele of TCF7L2 rs7903146 exhibit a diminished increase of insulin secretion in response to intravenous glucose to compensate for insulin resistance as induced by bed rest. Reduced paracrine glucagon stimulation may contribute to the impairment of beta-cell function in the carriers TCF7L2 rs7903146 T-allele associated with increased risk of type 2 diabetes.",
keywords = "Adult, Bed Rest, Blood Pressure, Body Mass Index, Carrier State, Diabetes Mellitus, Type 2, Genotype, Glucose Tolerance Test, Humans, Insulin, Insulin Resistance, Lipoproteins, Male, Reference Values, TCF Transcription Factors, Young Adult",
author = "Alibegovic, {Amra C} and Sonne, {Mette P} and Lise H{\o}jbjerre and Torben Hansen and Oluf Pedersen and {van Hall}, Gerrit and Holst, {Jens J} and Bente Stallknecht and Flemming Dela and Allan Vaag",
year = "2010",
month = "4",
day = "1",
doi = "10.2337/db09-0918",
language = "English",
volume = "59",
pages = "836--43",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "4",

}

Alibegovic, AC, Sonne, MP, Højbjerre, L, Hansen, T, Pedersen, O, van Hall, G, Holst, JJ, Stallknecht, B, Dela, F & Vaag, A 2010, 'The T-allele of TCF7L2 rs7903146 associates with a reduced compensation of insulin secretion for insulin resistance induced by 9 days of bed rest', Diabetes, bind 59, nr. 4, s. 836-43. https://doi.org/10.2337/db09-0918

The T-allele of TCF7L2 rs7903146 associates with a reduced compensation of insulin secretion for insulin resistance induced by 9 days of bed rest. / Alibegovic, Amra C; Sonne, Mette P; Højbjerre, Lise; Hansen, Torben; Pedersen, Oluf; van Hall, Gerrit; Holst, Jens J; Stallknecht, Bente; Dela, Flemming; Vaag, Allan.

I: Diabetes, Bind 59, Nr. 4, 01.04.2010, s. 836-43.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - The T-allele of TCF7L2 rs7903146 associates with a reduced compensation of insulin secretion for insulin resistance induced by 9 days of bed rest

AU - Alibegovic, Amra C

AU - Sonne, Mette P

AU - Højbjerre, Lise

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - van Hall, Gerrit

AU - Holst, Jens J

AU - Stallknecht, Bente

AU - Dela, Flemming

AU - Vaag, Allan

PY - 2010/4/1

Y1 - 2010/4/1

N2 - OBJECTIVE: The aim of this study was to determine whether the type 2 diabetes-associated T-allele of transcription factor 7-like 2 (TCF7L2) rs7903146 associates with impaired insulin secretion to compensate for insulin resistance induced by bed rest. RESEARCH DESIGN AND METHODS: A total of 38 healthy young Caucasian men were studied before and after bed rest using the hyperinsulinemic-euglycemic clamp technique combined with indirect calorimetry preceded by an intravenous glucose tolerance test. The TCF7L2 rs7903146 was genotyped using allelic discrimination performed with an ABI 7900 system. The genetic analyses were done assuming a dominant model of inheritance. RESULTS: The first-phase insulin response (FPIR) was significantly lower in carriers of the T-allele compared with carriers of the CC genotype before bed rest, with and without correction for insulin resistance. The incremental rise of FPIR in response to insulin resistance induced by bed rest was lower in carriers of the T-allele (P < 0.001). Fasting plasma glucagon levels were significantly lower in carriers of the T-allele before and after bed rest. While carriers of the CC genotype developed increased hepatic insulin resistance, the TCF7L2 rs7903146 did not influence peripheral insulin action or the rate of lipolysis before or after bed rest. CONCLUSIONS: Healthy carriers of the T-allele of TCF7L2 rs7903146 exhibit a diminished increase of insulin secretion in response to intravenous glucose to compensate for insulin resistance as induced by bed rest. Reduced paracrine glucagon stimulation may contribute to the impairment of beta-cell function in the carriers TCF7L2 rs7903146 T-allele associated with increased risk of type 2 diabetes.

AB - OBJECTIVE: The aim of this study was to determine whether the type 2 diabetes-associated T-allele of transcription factor 7-like 2 (TCF7L2) rs7903146 associates with impaired insulin secretion to compensate for insulin resistance induced by bed rest. RESEARCH DESIGN AND METHODS: A total of 38 healthy young Caucasian men were studied before and after bed rest using the hyperinsulinemic-euglycemic clamp technique combined with indirect calorimetry preceded by an intravenous glucose tolerance test. The TCF7L2 rs7903146 was genotyped using allelic discrimination performed with an ABI 7900 system. The genetic analyses were done assuming a dominant model of inheritance. RESULTS: The first-phase insulin response (FPIR) was significantly lower in carriers of the T-allele compared with carriers of the CC genotype before bed rest, with and without correction for insulin resistance. The incremental rise of FPIR in response to insulin resistance induced by bed rest was lower in carriers of the T-allele (P < 0.001). Fasting plasma glucagon levels were significantly lower in carriers of the T-allele before and after bed rest. While carriers of the CC genotype developed increased hepatic insulin resistance, the TCF7L2 rs7903146 did not influence peripheral insulin action or the rate of lipolysis before or after bed rest. CONCLUSIONS: Healthy carriers of the T-allele of TCF7L2 rs7903146 exhibit a diminished increase of insulin secretion in response to intravenous glucose to compensate for insulin resistance as induced by bed rest. Reduced paracrine glucagon stimulation may contribute to the impairment of beta-cell function in the carriers TCF7L2 rs7903146 T-allele associated with increased risk of type 2 diabetes.

KW - Adult

KW - Bed Rest

KW - Blood Pressure

KW - Body Mass Index

KW - Carrier State

KW - Diabetes Mellitus, Type 2

KW - Genotype

KW - Glucose Tolerance Test

KW - Humans

KW - Insulin

KW - Insulin Resistance

KW - Lipoproteins

KW - Male

KW - Reference Values

KW - TCF Transcription Factors

KW - Young Adult

U2 - 10.2337/db09-0918

DO - 10.2337/db09-0918

M3 - Journal article

C2 - 20107109

VL - 59

SP - 836

EP - 843

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 4

ER -