Because skeletal muscle plays a major role in glucose disposal, it may be the primary site of insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM). Rates of glycogen synthesis (GS), glucose utilization via glycolysis, glycolytic utilization (GU), and glucose transport (GT) were studied in epitrochlearis muscles (EMs) obtained from 10-wk-old nonfasted Sprague-Dawley rats in which NIDDM was neonatally induced with streptozocin. Plasma glucose in NIDDM rats was elevated (P < 0.001), whereas plasma insulin was similar in NIDDM and control rats. No differences in muscle weight, protein, glycogen, ATP, phosphocreatine, lactate, lactate-pyruvate ratios, or glucose-6-phosphate were noted in EMs of control and NIDDM rats. EMs were incubated in medium containing 5.6 or 11.2 mM glucose with tracer D-[5-3H]glucose and insulin from 0 to 7.18 × 10−7 M for 1 or 2 h, and GS, GT, and GU were evaluated. Similar rates of basal (non-insulin-mediated) and insulin-stimulated GS, GU, and GT were observed in EMs of NIDDM and control rats incubated in 5.6 mM glucose for 2 h. Insulin doseresponse curves revealed similar sensitivities and responsiveness. Increasing glucose concentration (from 5.6 to 11.2 mM) induced significant increases in basal rates of GS, GU, and GT in EMs of control but not NIDDM rats. Insulin dose-response curves for GS and GT revealed decreased sensitivity and no change in responsiveness in EMs of control and NIDDM rats, even though GU of EMs of NIDDM rats was significantly lower at basal and all other insulin concentrations. These data revealed that both insulin resistance and glucose resistance contribute to the impaired glucose metabolism in EMs of the NIDDM rat.
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Original Articles|
September 01 1990
Effect of Insulin on Glucose Utilization in Epitrochlearis Muscle of Rats With Streptozocin-Induced NIDDM Free
Irene E Karl;
Irene E Karl
Department of Internal Medicine, Endocrinology and Metabolism, Washington University School of Medicine
St. Louis, Missouri
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James R Gavin, III;
James R Gavin, III
Department of Internal Medicine, Endocrinology and Metabolism, Washington University School of Medicine
St. Louis, Missouri
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Joseph Levy
Joseph Levy
Department of Internal Medicine, Endocrinology and Metabolism, Washington University School of Medicine
St. Louis, Missouri
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Address correspondence and reprint requests to Irene E. Karl, PhD, Department of Internal Medicine, Endocrinology and Metabolism Division, Washington University School of Medicine, 660 South Euclid, Box 8127, St. Louis, MO 63110.
Diabetes 1990;39(9):1106–1115
Article history
Received:
November 20 1989
Revision Received:
April 25 1990
Accepted:
April 25 1990
PubMed:
2200730
Citation
Irene E Karl, James R Gavin, Joseph Levy; Effect of Insulin on Glucose Utilization in Epitrochlearis Muscle of Rats With Streptozocin-Induced NIDDM. Diabetes 1 September 1990; 39 (9): 1106–1115. https://doi.org/10.2337/diab.39.9.1106
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