Restoration of insulin responsiveness in skeletal muscle of morbidly obese patients after weight loss. Effect on muscle glucose transport and glucose transporter GLUT4.

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Jose F. Caro (Creator)

G. Lynis Dohm (Creator)

Charles W. Elton (Creator)

Jacob E. Friedman (Creator)

Nancy Leggett-Frazier (Creator)

Walter P. Pories (Creator)

Edward B. Tapscott (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: A major defect contributing to impaired insulin action in human obesity is reduced glucose transport activity in skeletal muscle. This study was designed to determine whether the improvement in whole body glucose disposal associated with weight reduction is related to a change in skeletal muscle glucose transport activity and levels of the glucose transporter protein GLUT4. Seven morbidly obese (body mass index = 45.8±2.5 mean ± SE) patients including four with non-insulin-dependent diabetes mellitus (NIDDM) underwent gastric bypass surgery for treatment of their obesity. In vivo glucose disposal during a euglycemic clamp at an insulin infusion rate of 40 mU/m2 per min was reduced to 27% of nonobese controls (P < 0.01) and improved to 78% of normal after weight loss of 43.1±3.1 kg (P < 0.01). Maximal insulin-stimulated glucose transport activity in incubated muscle fibers was reduced by ~ 50% in obese patients at the time of gastric bypass surgery but increased twofold (P < 0.01) to 88% of normal in five separate patients after similar weight reduction. Muscle biopsies obtained from vastus lateralis before and after weight loss revealed no significant change in levels of GLUT4 glucose transporter protein. These data demonstrate conclusively that insulin resistance in skeletal muscle of morbidly obese patients with and without NIDDM cannot be causally related to the cellular content of GLUT4 protein. The results further suggest that morbid obesity contributes to whole body insulin resistance through a reversible defect in skeletal muscle glucose transport activity. The mechanism for this improvement may involve enhanced transporter translocation and/or activation. Originally published Journal of Clinical Investigation Vol. 89 No. 2 Feb 1992

Additional Information

Publication

Other

Journal of Clinical Investigation. 89:2(February 1992) p. 701-705.

Language: English

Date: 2011

Keywords

Insulin resistance, Obesity, glucose disposal, Non-insulin-dependent diabetes, glucose metabolism

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