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

Mogher Khamaisi, Ruth Potashnik, Amir Tirosh, Eran Demshchak, Assaf Rudich, Hans Tritschler, Klaus Wessel, Nava Bashan

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

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 possibility 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. Gastrocnemius 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. Gastrocnemius 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 99.1 ± 5.0 μmol/g muscle). Insulin-stimulated 2-deoxyglucose (2 DG) uptake into isolated soleus muscle was reduced in diabetic rats compared with the control group (474 ± 15 v 568 ± 52 pmol/mg muscle · 30 min, respectively, P = .05). LA 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.

Original languageEnglish
Pages (from-to)763-768
Number of pages6
JournalMetabolism: Clinical and Experimental
Volume46
Issue number7
DOIs
StatePublished - 1 Jan 1997

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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