http://www.cnr.it/ontology/cnr/individuo/prodotto/ID30392
Common variants of the novel type 2 diabetes genes CDKAL1 and HHEX/IDE are associated with decreased pancreatic beta-cell function (Articolo in rivista)
- Type
- Label
- Common variants of the novel type 2 diabetes genes CDKAL1 and HHEX/IDE are associated with decreased pancreatic beta-cell function (Articolo in rivista) (literal)
- Anno
- 2007-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.2337/db07-0634 (literal)
- Alternative label
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Pascoe L; Tura A; Patel SK; Ibrahim IM; Ferrannini E; Zeggini E; Weedon MN; Mari A; Hattersley AT; McCarthy MI; Frayling TM; Walker M (literal)
- Pagina inizio
- Pagina fine
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
- Rivista
- Note
- ISI Web of Science (WOS) (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- 1, 4, 12: Diabetes Research Group, Newcastle University, Newcastle upon Tyne, U.K.
2, 8: CNR Institute of Biomedical Engineering, Padova, Italy
3: Cardiovascular Research Group, Department of Medicine, University of Melbourne, Melbourne, Australia
5: University of Pisa, School of Medicine, Pisa, Italy
6, 10: Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, and the Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.
7, 9, 11: Diabetes Genetics Group and Genetics of Complex Traits, Peninsula Medical School, Exeter, U.K. (literal)
- Titolo
- Common variants of the novel type 2 diabetes genes CDKAL1 and HHEX/IDE are associated with decreased pancreatic beta-cell function (literal)
- Abstract
- OBJECTIVE-- Type 2 diabetes is characterized by impaired
pancreatic beta-cell function and decreased insulin sensitivity.
Genome-wide association studies have identified common, novel
type 2 diabetes susceptibility loci within the FTO, CDKAL1,
CDKN2A/CDKN2B, IGF2BP2, HHEX/IDE, and SLC30A8 gene
regions. Our objective was to explore the relationships between
the diabetes-associated alleles and measures of beta-cell function
and whole-body insulin sensitivity.
RESEARCH DESIGN AND METHODS-- A total of 1,276
healthy subjects of European ancestry were studied at 19 centers.
Indexes of beta-cell function (including 30-min insulin response
and glucose sensitivity) were derived from a 75-g oral
glucose tolerance test, and whole-body insulin sensitivity (M/I)
was assessed by hyperinsulinemic-euglycemic clamp. Genotype/
phenotype relationships were studied by linear trend analysis
correcting for age, sex, and recruitment center.
RESULTS-- CDKAL1 and HHEX/IDE diabetes-associated alleles
were both associated with decreased 30-min insulin response
(both P = 0.0002) and decreased pancreatic beta-cell
glucose sensitivity (P = 9.86 x 10^(-5) and 0.009, respectively), and
these relationships remained after correction for M/I. The FTO
susceptibility allele showed a weak but consistent association
with increased adiposity, which in turn was linked to a decrease
in M/I. However, none of the other novel diabetes susceptibility
alleles were associated with insulin sensitivity.
CONCLUSIONS-- CDKAL1 and HHEX/IDE diabetes-associated
alleles are associated with decreased pancreatic beta-cell
function, including decreased beta-cell glucose sensitivity that relates
insulin secretion to plasma glucose concentration. We
confirmed the association between the FTO allele and increased
adiposity, but none of the other novel susceptibility alleles were
associated with whole-body insulin sensitivity. (literal)
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- Autore CNR
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