Lipoic acid reduces glycemia and increases muscle GLUT4 content in streptozotocin-diabetic rats

• Published in: Metabolism, clinical and experimental Vol. 46; no. 7; pp. 763 - 768
• Main Authors: Khamaisi, Mogher, Potashnik, Ruth, Tirosh, Amir, Demshchak, Eran, Rudich, Assaf, Trischler, Hans, Wessel, Klus, Bashan, Nava
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.1997; Elsevier
• Subjects: Animals; Biological and medical sciences; Blood Glucose - analysis; Deoxyglucose - pharmacokinetics; diabete; diabetes; Diabetes Mellitus, Experimental - metabolism; experimentacion; experimentation; Fundamental and applied biological sciences. Psychology; Glucose Transporter Type 4; In Vitro Techniques; Insulin - pharmacology; Intermediate and energetic metabolism; Lactic Acid - metabolism; Male; Metabolisms and neurohumoral controls; Monosaccharide Transport Proteins - genetics; Monosaccharide Transport Proteins - metabolism; Muscle Proteins; Muscle, Skeletal - metabolism; rat; rata; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Thioctic Acid - pharmacology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Biological properties; Lipoic acid; Animal model; Energy metabolism; Rat; Enzyme; Rodentia; Concentration; Glucose; Metabolism; Cofactor; Binding protein; Vertebrata; Mammalia; Enzymatic activity; Animal; Oxoglutarate dehydrogenase (lipoamide); Muscle; Oxidoreductases; Glycemia
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/S0026-0495(97)90120-7

Alpha lipoic acid (lipoate [LA]), a cofactor of α-ketodehydrogenase, exhibits unique antioxidant properties. Recent studies suggest a direct effect of LA on glucose metabolism in both human and experimental diabetes. This study examines the possbility that LA positively affects glucose homeostasis in streptozotocin (STZ)-induced diabetic rats by altering skeletal muscle glucose utilization. Blood glucose concentration in STZ-diabetic rats following 10 days of intraperitoneal (IP) injection of LA 30 mg/kg was reduced compared with that in vehicle-treated diabetic rats [495 ± 131 v 641 ± 125 mg/dL in fed state, P = .003, and 189 ± 48 v 341 ± 36 mg/dL after 12-hour fast, P = .001). No effect of LA on plasma insulin was observed. gastroenemius muscle crude membrane GLUT4 protein was elevated both in control and in diabetic rats treated with LA by 1.5- and 2.8-fold, respectively, without significant changes in GLUT4 mRNA levels. Gastroenemius lactic acid was increased in diabetic rats (19.9 ± 5.5 v 10.4 ± 2.8 μmol/g muscle, P < .05 v nondiabetic rats), and was normal in LA-treated diabetic rats (9.1 ± 5.0 μmol/g muscle). Insulin-stimulated 2-deoxyglucose (2 DG) uptake into isolated soleus muscle was reduced in treatment prevented this reduction, resulting in insulin-stimulated glucose uptake comparable to that of nondiabetic animals. These results suggest that daily LA treatment may reduce blood glucose concentrations in STZ-diabetic rats by enhancing muscle GLUT4 protein content and by increasing muscle glucose utilization.