Membrane glycoprotein PC-1, an inhibitor of insulin signaling, produces insulin resistance when overexpressed in cells transfected with PC-1 cDNA. In the present study, we determined whether PC-1 plays a role in the insulin resistance of skeletal muscle in obesity. Rectus abdominus muscle biopsies were taken from patients undergoing elective surgery. Subjects included both NIDDM patients (n = 14) and nondiabetic patients (n = 34) across a wide range of BMI values (19.5–90.1). Insulin-stimulated glucose transport was measured in incubated muscle strips, and PC-1 content, enzymatic activity, and insulin receptor content were measured in solubilized muscle extracts. Increasing BMI correlated with both an increase in the content of PC-1 in muscle (r = 0.55, P < 0.001) and a decrease in insulin stimulation of muscle glucose transport (r = −0.58, P = 0.008). NIDDM had no effect on either PC-1 content or glucose transport for any given level of obesity. Insulin stimulation of muscle glucose transport was negatively related to muscle PC-1 content (r = −0.68, P = 0.001) and positively related to insulin receptor content (r = 0.60, P = 0.005). Multivariate analysis indicated that both skeletal muscle PC-1 content and insulin receptor content, but not BMI, were independent predictors of insulin-stimulated glucose transport. Muscle PC-1 content accounted for 42% and insulin receptor content for 17% of the variance in glucose transport values. These studies raise the possibility that increased expression of PC-1 and a decreased insulin receptor content in skeletal muscle may be involved in the insulin resistance of obesity.
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Original Articles|
October 01 1996
Skeletal Muscle Content of Membrane Glycoprotein PC-1 in Obesity: Relationship to Muscle Glucose Transport
Jack F Youngren;
Jack F Youngren
Department of Medicine, Division of Diabetes and Endocrine Research, Mount Zion Medical Center, University of California San Francisco
San Francisco, California
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Betty A Maddux;
Betty A Maddux
Department of Medicine, Division of Diabetes and Endocrine Research, Mount Zion Medical Center, University of California San Francisco
San Francisco, California
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Shlomo Sasson;
Shlomo Sasson
Department of Medicine, Division of Diabetes and Endocrine Research, Mount Zion Medical Center, University of California San Francisco
San Francisco, California
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Paolo Sbraccia;
Paolo Sbraccia
Department of Medicine, Division of Diabetes and Endocrine Research, Mount Zion Medical Center, University of California San Francisco
San Francisco, California
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Edward B Tapscott;
Edward B Tapscott
Department of Biochemistry, School of Medicine, East Carolina University
Greenville, North Carolina
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Melvin S Swanson;
Melvin S Swanson
Department of Surgery, School of Medicine, East Carolina University
Greenville, North Carolina
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G Lynis Dohm;
G Lynis Dohm
Department of Medicine, Division of Diabetes and Endocrine Research, Mount Zion Medical Center, University of California San Francisco
San Francisco, California
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Ira D Goldfine
Ira D Goldfine
Department of Medicine, Division of Diabetes and Endocrine Research, Mount Zion Medical Center, University of California San Francisco
San Francisco, California
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Address correspondence and reprint requests to Dr. Jack F. Youngren, Division of Diabetes and Endocrine Research, UCSF Mount Zion Medical Center, RO. Box 7921, San Francisco, CA 94120. [email protected].
Diabetes 1996;45(10):1324–1328
Article history
Received:
January 29 1996
Revision Received:
May 23 1996
Accepted:
May 23 1996
PubMed:
8826966
Citation
Jack F Youngren, Betty A Maddux, Shlomo Sasson, Paolo Sbraccia, Edward B Tapscott, Melvin S Swanson, G Lynis Dohm, Ira D Goldfine; Skeletal Muscle Content of Membrane Glycoprotein PC-1 in Obesity: Relationship to Muscle Glucose Transport. Diabetes 1 October 1996; 45 (10): 1324–1328. https://doi.org/10.2337/diab.45.10.1324
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