The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men

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The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men. / Pilgaard, K; Jensen, C B; Schou, J H; Lyssenko, V; Wegner, L; Brøns, C; Vilsbøll, T; Hansen, T; Madsbad, S; Holst, Jens Juul; Vølund, A; Poulsen, P; Groop, L; Vaag, A A.

In: Diabetologia, Vol. 52, No. 7, 07.2009, p. 1298-307.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Pilgaard, K, Jensen, CB, Schou, JH, Lyssenko, V, Wegner, L, Brøns, C, Vilsbøll, T, Hansen, T, Madsbad, S, Holst, JJ, Vølund, A, Poulsen, P, Groop, L & Vaag, AA 2009, 'The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men', Diabetologia, vol. 52, no. 7, pp. 1298-307. https://doi.org/10.1007/s00125-009-1307-x

APA

Pilgaard, K., Jensen, C. B., Schou, J. H., Lyssenko, V., Wegner, L., Brøns, C., ... Vaag, A. A. (2009). The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men. Diabetologia, 52(7), 1298-307. https://doi.org/10.1007/s00125-009-1307-x

Vancouver

Pilgaard K, Jensen CB, Schou JH, Lyssenko V, Wegner L, Brøns C et al. The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men. Diabetologia. 2009 Jul;52(7):1298-307. https://doi.org/10.1007/s00125-009-1307-x

Author

Pilgaard, K ; Jensen, C B ; Schou, J H ; Lyssenko, V ; Wegner, L ; Brøns, C ; Vilsbøll, T ; Hansen, T ; Madsbad, S ; Holst, Jens Juul ; Vølund, A ; Poulsen, P ; Groop, L ; Vaag, A A. / The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men. In: Diabetologia. 2009 ; Vol. 52, No. 7. pp. 1298-307.

Bibtex

@article{e25c49aedd98425ea19cf45da7c8fa2d,
title = "The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men",
abstract = "AIMS/HYPOTHESIS: We studied the physiological, metabolic and hormonal mechanisms underlying the elevated risk of type 2 diabetes in carriers of TCF7L2 gene.METHODS: We undertook genotyping of 81 healthy young Danish men for rs7903146 of TCF7L2 and carried out various beta cell tests including: 24 h glucose, insulin and glucagon profiles; OGTT; mixed meal test; IVGTT; hyperglycaemic clamp with co-infusion of glucagon-like peptide (GLP)-1 or glucose-dependent insulinotropic polypeptide (GIP); and a euglycaemic-hyperinsulinaemic clamp combined with glucose tracer infusion to study hepatic and peripheral insulin action.RESULTS: Carriers of the T allele were characterised by reduced 24 h insulin concentrations (p < 0.05) and reduced insulin secretion relative to glucose during a mixed meal test (beta index: p < 0.003), but not during an IVGTT. This was further supported by reduced late-phase insulinotropic action of GLP-1 (p = 0.03) and GIP (p = 0.07) during a 7 mmol/l hyperglycaemic clamp. Secretion of GLP-1 and GIP during the mixed meal test was normal. Despite elevated hepatic glucose production, carriers of the T allele had significantly reduced 24 h glucagon concentrations (p < 0.02) suggesting altered alpha cell function.CONCLUSIONS/INTERPRETATION: Elevated hepatic glucose production and reduced insulinotropic effect of incretin hormones contribute to an increased risk of type 2 diabetes in carriers of the rs7903146 risk T allele of TCF7L2.",
keywords = "Adolescent, Alleles, Blood Glucose, Diabetes Mellitus, Type 2, Genotype, Glucagon-Like Peptide 1, Glucose Clamp Technique, Glucose Tolerance Test, Glutaminase, Humans, Hyperinsulinism, Incretins, Insulin, Intracellular Signaling Peptides and Proteins, Liver, Male, Risk Factors, TCF Transcription Factors, Transcription Factor 7-Like 2 Protein, Tritium, Young Adult",
author = "K Pilgaard and Jensen, {C B} and Schou, {J H} and V Lyssenko and L Wegner and C Br{\o}ns and T Vilsb{\o}ll and T Hansen and S Madsbad and Holst, {Jens Juul} and A V{\o}lund and P Poulsen and L Groop and Vaag, {A A}",
year = "2009",
month = "7",
doi = "10.1007/s00125-009-1307-x",
language = "English",
volume = "52",
pages = "1298--307",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer",
number = "7",

}

RIS

TY - JOUR

T1 - The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men

AU - Pilgaard, K

AU - Jensen, C B

AU - Schou, J H

AU - Lyssenko, V

AU - Wegner, L

AU - Brøns, C

AU - Vilsbøll, T

AU - Hansen, T

AU - Madsbad, S

AU - Holst, Jens Juul

AU - Vølund, A

AU - Poulsen, P

AU - Groop, L

AU - Vaag, A A

PY - 2009/7

Y1 - 2009/7

N2 - AIMS/HYPOTHESIS: We studied the physiological, metabolic and hormonal mechanisms underlying the elevated risk of type 2 diabetes in carriers of TCF7L2 gene.METHODS: We undertook genotyping of 81 healthy young Danish men for rs7903146 of TCF7L2 and carried out various beta cell tests including: 24 h glucose, insulin and glucagon profiles; OGTT; mixed meal test; IVGTT; hyperglycaemic clamp with co-infusion of glucagon-like peptide (GLP)-1 or glucose-dependent insulinotropic polypeptide (GIP); and a euglycaemic-hyperinsulinaemic clamp combined with glucose tracer infusion to study hepatic and peripheral insulin action.RESULTS: Carriers of the T allele were characterised by reduced 24 h insulin concentrations (p < 0.05) and reduced insulin secretion relative to glucose during a mixed meal test (beta index: p < 0.003), but not during an IVGTT. This was further supported by reduced late-phase insulinotropic action of GLP-1 (p = 0.03) and GIP (p = 0.07) during a 7 mmol/l hyperglycaemic clamp. Secretion of GLP-1 and GIP during the mixed meal test was normal. Despite elevated hepatic glucose production, carriers of the T allele had significantly reduced 24 h glucagon concentrations (p < 0.02) suggesting altered alpha cell function.CONCLUSIONS/INTERPRETATION: Elevated hepatic glucose production and reduced insulinotropic effect of incretin hormones contribute to an increased risk of type 2 diabetes in carriers of the rs7903146 risk T allele of TCF7L2.

AB - AIMS/HYPOTHESIS: We studied the physiological, metabolic and hormonal mechanisms underlying the elevated risk of type 2 diabetes in carriers of TCF7L2 gene.METHODS: We undertook genotyping of 81 healthy young Danish men for rs7903146 of TCF7L2 and carried out various beta cell tests including: 24 h glucose, insulin and glucagon profiles; OGTT; mixed meal test; IVGTT; hyperglycaemic clamp with co-infusion of glucagon-like peptide (GLP)-1 or glucose-dependent insulinotropic polypeptide (GIP); and a euglycaemic-hyperinsulinaemic clamp combined with glucose tracer infusion to study hepatic and peripheral insulin action.RESULTS: Carriers of the T allele were characterised by reduced 24 h insulin concentrations (p < 0.05) and reduced insulin secretion relative to glucose during a mixed meal test (beta index: p < 0.003), but not during an IVGTT. This was further supported by reduced late-phase insulinotropic action of GLP-1 (p = 0.03) and GIP (p = 0.07) during a 7 mmol/l hyperglycaemic clamp. Secretion of GLP-1 and GIP during the mixed meal test was normal. Despite elevated hepatic glucose production, carriers of the T allele had significantly reduced 24 h glucagon concentrations (p < 0.02) suggesting altered alpha cell function.CONCLUSIONS/INTERPRETATION: Elevated hepatic glucose production and reduced insulinotropic effect of incretin hormones contribute to an increased risk of type 2 diabetes in carriers of the rs7903146 risk T allele of TCF7L2.

KW - Adolescent

KW - Alleles

KW - Blood Glucose

KW - Diabetes Mellitus, Type 2

KW - Genotype

KW - Glucagon-Like Peptide 1

KW - Glucose Clamp Technique

KW - Glucose Tolerance Test

KW - Glutaminase

KW - Humans

KW - Hyperinsulinism

KW - Incretins

KW - Insulin

KW - Intracellular Signaling Peptides and Proteins

KW - Liver

KW - Male

KW - Risk Factors

KW - TCF Transcription Factors

KW - Transcription Factor 7-Like 2 Protein

KW - Tritium

KW - Young Adult

U2 - 10.1007/s00125-009-1307-x

DO - 10.1007/s00125-009-1307-x

M3 - Journal article

VL - 52

SP - 1298

EP - 1307

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 7

ER -

ID: 153104635