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      Glucose and lipid metabolism in young lean normotensive males with the G protein beta3 825T-allele.

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          Abstract

          The 825T-allele of the C825T polymorphism in GNB3, the gene for the G protein beta3 subunit, has been reported to be associated with essential hypertension and obesity. Expression of Gbeta3s, the gene product of GNB3 associated with the GNB3 825T-allele, causes increased signal transduction which may contribute to pathogenetic mechanisms ultimately resulting in hypertension and obesity. Given the known involvement of heterotrimeric G proteins in insulin secretion and insulin action on the cellular level, we analysed insulin sensitivity in each 15 young lean normotensive males with TC- and CC-genotypes, respectively. Blood glucose and serum insulin samples were taken during a standard oral glucose tolerance test. Insulin-stimulated glucose disposal was analysed by euglycemic-hyperinsulinemic clamp. Both groups did not differ with regard to the time-courses for glucose or insulin concentrations in the oral glucose tolerance test. Furthermore, insulin-stimulated glucose disposal was virtually independent of genotype. The TC-genotype is not associated with a primary defect in insulin secretion or sensitivity suggesting that obesity and hypertension in carriers of 825T do not likely result from primary alterations in glucose and insulin homeostasis. However, GNB3 825T-associated obesity may predispose to insulin resistance, an issue which remains to be investigated. Furthermore, fasting cholesterol was significantly higher in TC compared to CC genotype (4.71 versus 3.96 mmol/l; p = 0.007) suggesting that enhanced G protein signalling might be associated with alterations of cholesterol metabolism.

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          Author and article information

          Journal
          Eur. J. Med. Res.
          European journal of medical research
          0949-2321
          0949-2321
          Mar 27 2003
          : 8
          : 3
          Affiliations
          [1 ] Abteilung für Endokrinologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Germany.
          Article
          12730030
          8cece06e-7dc5-47bf-98be-26b533749169
          History

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