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The T allele of rs7...
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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Pilgaard, K. (author)
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Jensen, C. B. (author)
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Schou, J. H. (author)
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- Lyssenko, Valeriya (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Wegner, L. (author)
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Brons, C. (author)
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Vilsboll, T. (author)
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Hansen, T. (author)
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Madsbad, S. (author)
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Holst, J. J. (author)
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Volund, A. (author)
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Poulsen, P. (author)
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- Groop, Leif (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Pedersen, O. (author)
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Vaag, A. A. (author)
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(creator_code:org_t)
- 2009-03-14
- 2009
- English.
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In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 52:7, s. 1298-1307
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Abstract
Subject headings
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- We studied the physiological, metabolic and hormonal mechanisms underlying the elevated risk of type 2 diabetes in carriers of TCF7L2 gene. 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. 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. 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Type 2 diabetes
- TCF7L2
- Insulin secretion
- Incretin hormones
- Hepatic glucose production
- Genetics
- Glucagon
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Pilgaard, K.
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Jensen, C. B.
-
Schou, J. H.
-
Lyssenko, Valeri ...
-
Wegner, L.
-
Brons, C.
-
show more...
-
Vilsboll, T.
-
Hansen, T.
-
Madsbad, S.
-
Holst, J. J.
-
Volund, A.
-
Poulsen, P.
-
Groop, Leif
-
Pedersen, O.
-
Vaag, A. A.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Diabetologia
- By the university
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Lund University