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

K Pilgaard; C Jensen; J Schou; V Lyssenko; L Wegner; C Brøns; T Vilsbøll; T Hansen; S Madsbad; J Holst; A Vølund; P Poulsen; L Groop; Oluf Pedersen; A Vaag; K Pilgaard; C B Jensen; J H Schou; V Lyssenko; L Wegner; C Brøns; Tina Vilsbøll; T Hansen; S Madsbad; Jens Møller Holst; Anders Vølund; P Poulsen; L Groop; O Pedersen; Allan Vaag

doi:10.1007/s00125-009-1307-x

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

K Pilgaard, C Jensen, J Schou, V Lyssenko, L Wegner, C Brøns, T Vilsbøll, T Hansen, S Madsbad, J Holst, A Vølund, P Poulsen, L Groop, Oluf Pedersen, A Vaag, K Pilgaard, C B Jensen, J H Schou, V Lyssenko, L WegnerC Brøns, Tina Vilsbøll, T Hansen, S Madsbad, Jens Møller Holst, Anders Vølund, P Poulsen, L Groop, O Pedersen, Allan Vaag

108 Citationer (Scopus)

Abstract

Udgivelsesdato: 2009-Mar-14

Originalsprog	Engelsk
Tidsskrift	Diabetologia
Vol/bind	52
Udgave nummer	7
Sider (fra-til)	1298-307
Antal sider	10
ISSN	0012-186X
DOI	https://doi.org/10.1007/s00125-009-1307-x https://doi.org/10.1007/s00125-009-1307-x
Status	Udgivet - 1 jul. 2009

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Citationsformater

Pilgaard, K., Jensen, C., Schou, J., Lyssenko, V., Wegner, L., Brøns, C., Vilsbøll, T., Hansen, T., Madsbad, S., Holst, J., Vølund, A., Poulsen, P., Groop, L., Pedersen, O., Vaag, A., Pilgaard, K., Jensen, C. B., Schou, J. H., Lyssenko, V., ... Vaag, 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, https://doi.org/10.1007/s00125-009-1307-x

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; Schou, J et al.
I: Diabetologia, Bind 52, Nr. 7, 01.07.2009, s. 1298-307.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Pilgaard, K, Jensen, C, Schou, J, Lyssenko, V, Wegner, L, Brøns, C, Vilsbøll, T, Hansen, T, Madsbad, S , Holst, J, Vølund, A, Poulsen, P, Groop, L, Pedersen, O , Vaag, A, Pilgaard, K, Jensen, CB, Schou, JH, Lyssenko, V, Wegner, L, Brøns, C, Vilsbøll, T, Hansen, T, Madsbad, S, Holst, JM, Vølund, A, Poulsen, P, Groop, L, Pedersen, O & Vaag, 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, bind 52, nr. 7, s. 1298-307. https://doi.org/10.1007/s00125-009-1307-x, https://doi.org/10.1007/s00125-009-1307-x

Pilgaard K, Jensen C, Schou J, 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. 1;52(7):1298-307. doi: 10.1007/s00125-009-1307-x, 10.1007/s00125-009-1307-x

@article{baec7f702d9211de9f0a000ea68e967b,

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.",

author = "K Pilgaard and C Jensen and J Schou and V Lyssenko and L Wegner and C Br{\o}ns and T Vilsb{\o}ll and T Hansen and S Madsbad and J Holst and A V{\o}lund and P Poulsen and L Groop and Oluf Pedersen and A Vaag and K Pilgaard and Jensen, {C B} and Schou, {J H} and V Lyssenko and L Wegner and C Br{\o}ns and Tina Vilsb{\o}ll and T Hansen and S Madsbad and Holst, {Jens M{\o}ller} and Anders V{\o}lund and P Poulsen and L Groop and O Pedersen and Allan Vaag",

note = "Cited By (since 1996): 2Export Date: 4 November 2009Source: Scopus",

year = "2009",

month = jul,

day = "1",

doi = "10.1007/s00125-009-1307-x",

language = "English",

volume = "52",

pages = "1298--307",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer",

number = "7",

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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

AU - Schou, J

AU - Lyssenko, V

AU - Wegner, L

AU - Brøns, C

AU - Vilsbøll, T

AU - Hansen, T

AU - Madsbad, S

AU - Holst, J

AU - Vølund, A

AU - Poulsen, P

AU - Groop, L

AU - Pedersen, Oluf

AU - Vaag, A

AU - Pilgaard, K

AU - Jensen, C B

AU - Schou, J H

AU - Lyssenko, V

AU - Wegner, L

AU - Brøns, C

AU - Vilsbøll, Tina

AU - Hansen, T

AU - Madsbad, S

AU - Holst, Jens Møller

AU - Vølund, Anders

AU - Poulsen, P

AU - Groop, L

AU - Pedersen, O

AU - Vaag, Allan

N1 - Cited By (since 1996): 2Export Date: 4 November 2009Source: Scopus

PY - 2009/7/1

Y1 - 2009/7/1

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.

U2 - 10.1007/s00125-009-1307-x

DO - 10.1007/s00125-009-1307-x

M3 - Journal article

C2 - 19288077

SN - 0012-186X

VL - 52

SP - 1298

EP - 1307

JO - Diabetologia

JF - Diabetologia

IS - 7

ER -