Promoter Polymorphisms −359T/C and −303A/G of the Catalytic Subunit p110β Gene of Human Phosphatidylinositol 3-Kinase Are Not Associated With Insulin Secretion or Insulin Sensitivity in Finnish Subjects
- Maija Kossila12,
- Jussi Pihlajamäki, MD2,
- Päivi Kärkkäinen, MSC2,
- Raija Miettinen, MSC2,
- Päivi Kekäläinen, MD2,
- Ilkka Vauhkonen, MD2,
- Seppo Ylä-Herttuala, MD12 and
- Markku Laakso, MD2
- 1A.I. Virtanen Institute for Molecular Sciences, Kuopio
- 2Department of Medicine, University of Kuopio, Kuopio, Finland
Abstract
OBJECTIVE—Phosphatidylinositol (PI) 3-kinase activity is required for insulin-stimulated translocation of GLUT4 transporters and glucose uptake and utilization. Therefore, genes encoding the subunits of PI 3-kinase are promising candidate genes for insulin resistance and type 2 diabetes. We recently cloned the catalytic subunit p110β gene of human PI 3-kinase and reported two nucleotide polymorphisms, −359T/C and −303A/G, in the promoter region of this gene. In this study, we determined the effects of these polymorphisms on insulin secretion and insulin sensitivity.
RESEARCH DESIGN AND METHODS—We studied two separate groups of Finnish nondiabetic subjects. Insulin secretion was evaluated by intravenous glucose tolerance test and insulin sensitivity by hyperinsulinemic-euglycemic clamp.
RESULTS—Our results showed that the −359T/C and −303A/G polymorphisms did not have a significant effect on fasting plasma insulin levels, insulin secretion, or insulin sensitivity.
CONCLUSIONS—It is unlikely that the promoter polymorphisms −359T/C and −303A/G of the catalytic subunit p110β gene of human PI 3-kinase have a major impact on insulin secretion, insulin sensitivity, or the risk of type 2 diabetes in Finnish subjects.
- IVGTT, intravenous glucose tolerance test
- OGTT, oral glucose tolerance test
- PI, phosphatidylinositol
- SG, glucose effectiveness
- SI, insulin sensitivity index
- WBGU, whole-body glucose uptake
Footnotes
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Address correspondence and reprint requests to Markku Laakso, Department of Medicine, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. E-mail: markku.laakso{at}kuh.fi.
Received for publication 2 April 2002 and accepted in revised form 29 September 2002.
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