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The common SLC30A8 ...
The common SLC30A8 Arg325Trp variant is associated with reduced first-phase insulin release in 846 non-diabetic offspring of type 2 diabetes patients--the EUGENE2 study
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Boesgaard, T. W. (author)
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Zilinskaite, J. (author)
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Vanttinen, M. (author)
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Laakso, M. (author)
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- Jansson, Per-Anders, 1961 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Hammarstedt, Ann, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Smith, Ulf, 1943 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Stefan, N. (author)
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Fritsche, A. (author)
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Haring, H. (author)
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Hribal, M. (author)
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Sesti, G. (author)
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Zobel, D. P. (author)
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Pedersen, O. (author)
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Hansen, T. (author)
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(creator_code:org_t)
- 2008-03-07
- 2008
- English.
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 51:5, s. 816-20
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- AIMS/HYPOTHESIS: A recent genome-wide association study identified the SLC30A8 rs13266634 polymorphism encoding an Arg325Trp polymorphism in the zinc transporter protein member 8 (ZnT-8) to be associated with type 2 diabetes. Here, we investigate whether the polymorphism is related to altered insulin release in response to intravenous and oral glucose loads in non-diabetic offspring of type 2 diabetic patients. METHODS: We genotyped SLC30A8 rs13266634 in 846 non-diabetic offspring of type 2 diabetic patients from five different white populations: Danish (n = 271), Finnish (n = 217), German (n = 149), Italian (n = 109) and Swedish (n = 100). Participants were subjected to both IVGTTs and OGTTs, and measurements of insulin sensitivity. RESULTS: Homozygous carriers of the major type 2 diabetes C risk-allele showed a 19% decrease in first-phase insulin release (0-10 min) measured during the IVGTT (CC 3,624 +/- 3,197; CT 3,763 +/- 2,674; TT 4,478 +/- 3,032 pmol l(-1) min(-1), mean +/- SD; p = 0.007). We found no significant genotype effect on insulin release measured during the OGTT or on estimates of insulin sensitivity. CONCLUSIONS/INTERPRETATION: Of European non-diabetic offspring of type 2 diabetes patients, 46% are homozygous carriers of the Arg325Trp polymorphism in ZnT-8, which is known to associate with type 2 diabetes. These diabetes-prone offspring are characterised by a 19% decrease in first-phase insulin release following an intravenous glucose load, suggesting a role for this variant in the pathogenesis of pancreatic beta cell dysfunction.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Adult
- Amino Acid Substitution
- Carrier State
- Cation Transport Proteins/*genetics
- Diabetes Mellitus
- Type 2/*genetics
- Female
- Genotype
- Homozygote
- Humans
- Insulin/*secretion
- Male
- Middle Aged
- Nuclear Family
- Reference Values
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Boesgaard, T. W.
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Zilinskaite, J.
-
Vanttinen, M.
-
Laakso, M.
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Jansson, Per-And ...
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Hammarstedt, Ann ...
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show more...
-
Smith, Ulf, 1943
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Stefan, N.
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Fritsche, A.
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Haring, H.
-
Hribal, M.
-
Sesti, G.
-
Zobel, D. P.
-
Pedersen, O.
-
Hansen, T.
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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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University of Gothenburg