title: Effects of oleanolic acid on the insulin signaling pathway in skeletal muscle of streptozotocin-induced diabetic male Sprague-Dawley rats.
abstract: BACKGROUND
  The pant-derived triterpene oleanolic acid (OA) has been shown to have antidiabetic effects, but its action on the insulin signaling cascade has not been fully elucidated. The aim of the present study was to investigate the effects of OA on aspects of the phosphatidylinositol 3-kinase/Akt insulin signaling cascade in skeletal muscle of streptozotocin-induced type 1 diabetic male Sprague-Dawley rats.
  
  
  METHODS
  Diabetic and non-diabetic rats were treated with insulin (4 IU/kg), OA (80 mg/kg), and the combination of OA + insulin in acute 60-min and sub-chronic 14-day studies. Single and daily doses were administered in the acute and sub-chronic studies, respectively. In acute studies, phosphorylated (p-) Akt and p-glycogen synthase (GS) expression was evaluated. In sub-chronic studies, GS and glycogen phosphorylase (GP) expression and activity were evaluated, as were glycogen levels.
  
  
  RESULTS
  The findings show that OA enhances insulin-stimulated hypoglycemic effects in diabetic rats. In the acute study, OA increased levels of p-Akt and decreased levels of p-GS. In the sub-chronic study, OA increased both GS and GP activity, whereas OA + insulin increased GS and decreased GP activity. Treatment of rats with OA and OA + insulin increased GS expression in the skeletal muscle of diabetic rats and decreased GP expression. Glycogen levels were increased by OA but decreased OA + insulin treatment.
  
  
  CONCLUSIONS
  Oleanolic acid in synergy with insulin can enhance activation of the insulin signaling pathway. Furthermore, the present study provides evidence of OA activation of insulin signaling enzymes independent of insulin.
authors.affiliation: Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Durban, South Africa.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mukundwa
authors.affiliation: Discipline of Biological Sciences, School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Durban, South Africa.
authors.forename: Samson
authors.initials: S
authors.lastname: Mukaratirwa
authors.affiliation: Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Durban, South Africa.
authors.forename: Bubuya
authors.initials: B
authors.lastname: Masola
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000378:metabolism; D024981:Glycogen Phosphorylase / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009828:Oleanolic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D009828:Oleanolic Acid; D006003:Glycogen; D024981:Glycogen Phosphorylase; D006006:Glycogen Synthase
keywords: 1型糖尿病; Rattus muscle; insulin signaling enzymes; oleanolic acid; type 1 diabetes; 大鼠肌肉; 胰岛素信号酶; 齐墩果酸