Effects of oleanolic acid on the insulin signaling pathway in skeletal muscle of streptozotocin-induced diabetic male Sprague-Dawley rats. 2016

Andrew Mukundwa, and Samson Mukaratirwa, and Bubuya Masola
Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Durban, South Africa.

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.

UI MeSH Term Description Entries
D007004 Hypoglycemic Agents Substances which lower blood glucose levels. Antidiabetic,Antidiabetic Agent,Antidiabetic Drug,Antidiabetics,Antihyperglycemic,Antihyperglycemic Agent,Hypoglycemic,Hypoglycemic Agent,Hypoglycemic Drug,Antidiabetic Agents,Antidiabetic Drugs,Antihyperglycemic Agents,Antihyperglycemics,Hypoglycemic Drugs,Hypoglycemic Effect,Hypoglycemic Effects,Hypoglycemics,Agent, Antidiabetic,Agent, Antihyperglycemic,Agent, Hypoglycemic,Agents, Antidiabetic,Agents, Antihyperglycemic,Agents, Hypoglycemic,Drug, Antidiabetic,Drug, Hypoglycemic,Drugs, Antidiabetic,Drugs, Hypoglycemic,Effect, Hypoglycemic,Effects, Hypoglycemic
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D008297 Male Males
D009828 Oleanolic Acid A pentacyclic triterpene that occurs widely in many PLANTS as the free acid or the aglycone for many SAPONINS. It is biosynthesized from lupane. It can rearrange to the isomer, ursolic acid, or be oxidized to taraxasterol and amyrin. Oleanol,Hederins,Oleanane Triterpenes,Triterpenes, Oleanane
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D005951 Glucose Tolerance Test A test to determine the ability of an individual to maintain HOMEOSTASIS of BLOOD GLUCOSE. It includes measuring blood glucose levels in a fasting state, and at prescribed intervals before and after oral glucose intake (75 or 100 g) or intravenous infusion (0.5 g/kg). Intravenous Glucose Tolerance,Intravenous Glucose Tolerance Test,OGTT,Oral Glucose Tolerance,Oral Glucose Tolerance Test,Glucose Tolerance Tests,Glucose Tolerance, Oral
D006003 Glycogen
D006006 Glycogen Synthase An enzyme that catalyzes the transfer of D-glucose from UDPglucose into 1,4-alpha-D-glucosyl chains. EC 2.4.1.11. Glycogen (Starch) Synthase,Glycogen Synthetase,Glycogen Synthase I,Synthase D,Synthase I,UDP-Glucose Glycogen Glucosyl Transferase,Synthase, Glycogen,Synthetase, Glycogen,UDP Glucose Glycogen Glucosyl Transferase
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015153 Blotting, Western Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes. Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings

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