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This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/E92    most recent 00617.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Pendergrass, M. Articles by DeFronzo, R. A. Search for Related Content PubMed PubMed Citation Articles by Pendergrass, M. Articles by DeFronzo, R. A.

Muscle glucose transport and phosphorylation in type 2 diabetic, obese nondiabetic, and genetically predisposed individuals

¹University of Texas Health Science Center, San Antonio, Texas; ²Department of Information Engineering, University of Padova, Padua; and ³Division of Endocrinology and Metabolic Diseases, Verona School of Medicine, Verona, Italy

Submitted 6 December 2005 ; accepted in final form 21 July 2006

Our objectives were to quantitate insulin-stimulated inward glucose transport and glucose phosphorylation in forearm muscle in lean and obese nondiabetic subjects, in lean and obese type 2 diabetic (T2DM) subjects, and in normal glucose-tolerant, insulin-resistant offspring of two T2DM parents. Subjects received a euglycemic insulin (40 mU·m^–2·min^–1) clamp with brachial artery/deep forearm vein catheterization. After 120 min of hyperinsulinemia, a bolus of D-mannitol/3-O-methyl-D-[¹⁴C]glucose/D-[3-³H]glucose (triple-tracer technique) was given into brachial artery and deep vein samples obtained every 12–30 s for 15 min. Insulin-stimulated forearm glucose uptake (FGU) and whole body glucose metabolism (M) were reduced by 40–50% in obese nondiabetic, lean T2DM, and obese T2DM subjects (all P < 0.01); in offspring, the reduction in FGU and M was 30% (P < 0.05). Inward glucose transport and glucose phosphorylation were decreased by 40–50% (P < 0.01) in obese nondiabetic and T2DM groups and closely paralleled the decrease in FGU. The intracellular glucose concentration in the space accessible to glucose was significantly greater in obese nondiabetic, lean T2DM, obese T2DM, and offspring compared with lean controls. We conclude that 1) obese nondiabetic, lean T2DM, and offspring manifest moderate-to-severe muscle insulin resistance (FGU and M) and decreased insulin-stimulated glucose transport and glucose phosphorylation in forearm muscle; these defects in insulin action are not further reduced by the combination of obesity plus T2DM; and 2) the increase in intracelullar glucose concentration under hyperinsulinemic euglycemic conditions in obese and T2DM groups suggests that the defect in glucose phosphorylation exceeds the defect in glucose transport.

insulin resistance; muscle; glucose phosphorylation; type 2 diabetes; obesity