oleanolic acid reduces hyperglycemia beyond treatment period with aktfoxo1-induced suppression of hepatic gluconeogenesis in type-2 diabetic mice齐墩果酸降低高血糖治疗期之外与aktfoxo1-induced抑制2型糖尿病小鼠的肝醣类.pdfVIP

Oleanolic Acid Reduces Hyperglycemia beyond Treatment Period with Akt/FoxO1-Induced Suppression of Hepatic Gluconeogenesis in Type-2 Diabetic Mice 1 1 2 2 1 Xiao-Yi Zeng , Yi-Ping Wang , James Cantley , Tristan J. Iseli , Juan Carlos Molero , 2 2 3 1,2,3 Bronwyn D. Hegarty , Edward W. Kraegen , Yang Ye , Ji-Ming Ye * 1 Molecular Pharmacology for Diabetes, Health Innovations Research Institute and School of Health Sciences, RMIT University, Melbourne, Victoria, Australia, 2 Diabetes and Obesity Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia, 3 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China Abstract The present study investigated the chronic efficacy of oleanolic acid (OA), a triterpenoid selected from our recent screening, on hyperglycemia in type-2 diabetic mice. C57BL/6J mice were fed a high-fat diet followed by low doses of streptozotocin to generate a type-2 diabetic model. OA (100 mg/kg/day) was administered orally for 2 weeks with its effects monitored for 6 weeks. High-fat feeding and streptozotocin generated a steady hyperglycemia (21.2 61.1 mM) but OA administration reversed the hyperglycemia by ,60%. Interestingly, after the cessation of OA administration, the reversed hyperglycemia was sustained for the entire post-treatment period of the study (4 weeks) despite the reoccurrence of dyslipidemia. Examination of insulin secretion and pancreas morphology did not indicate improved b-cell function as a likely mechanism. Urine glucose loss was decreased with substantial improvement of diabetic nephropathy after the OA t