title: Ursolic acid and rosiglitazone combination improves insulin sensitivity by increasing the skeletal muscle insulin-stimulated IRS-1 tyrosine phosphorylation in high-fat diet-fed C57BL/6J mice.
abstract: The aim of this present study was to investigate the effect of ursolic acid (UA) and rosiglitazone (RSG) on insulin sensitivity and proximal insulin signaling pathways in high-fat diet (HFD)-fed C57/BL/6J mice. Male C57BL/6J mice were fed either normal diet or HFD for 10 weeks, after which animals in each dietary group were divided into the following six groups (normal diet, normal diet plus UA and RSG, HFD alone, HFD plus UA, HFD plus RSG, and HFD plus UA and RSG) for the next 5 weeks. UA (5 mg/kg BW) and RSG (4 mg/kg BW) were administered as suspensions directly into the stomach using a gastric tube. The HFD diet elevated fasting plasma glucose, insulin, and homeostasis model assessment index. The expression of insulin receptor substrate (IRS)-1, phosphoinositide 3-kinase (PI3-kinase), Akt, and glucose transporter (GLUT) 4 were determined by Western blot analyses. The results demonstrated that combination treatment (UA/RSG) ameliorated HFD-induced glucose intolerance and insulin resistance by improving the homeostatic model assessment (HOMA) index. Further, combination treatment (UA/RSG) stimulated the IRS-1, PI3-kinase, Akt, and GLUT 4 translocation. These results strongly suggest that combination treatment (UA/RSG) activates IRS-PI3-kinase-Akt-dependent signaling pathways to induce GLUT 4 translocation and increases the expression of insulin receptor to improve glucose intolerance.
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, 608 002, Tamil Nadu, India.
authors.forename: Arjunan
authors.initials: A
authors.lastname: Sundaresan
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, 608 002, Tamil Nadu, India.
authors.forename: Thangaiyan
authors.initials: T
authors.lastname: Radhiga
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, 608 002, Tamil Nadu, India. pugalendipugalendi27@gmail.com.
authors.forename: Kodukkur Viswanathan
authors.initials: KV
authors.lastname: Pugalendi
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D004359:Drug Therapy, Combination / Q000009:adverse effects; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D055504:Insulin Receptor Substrate Proteins / Q000819:agonists* / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009765:Obesity / Q000139:chemically induced / Q000150:complications; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D000077154:Rosiglitazone; D015290:Second Messenger Systems / Q000187:drug effects; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*; D014315:Triterpenes / Q000009:adverse effects / Q000627:therapeutic use*; D015430:Weight Gain / Q000187:drug effects; D000097245:Ursolic Acid
chemical_list: D019440:Anti-Obesity Agents; D000975:Antioxidants; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D055504:Insulin Receptor Substrate Proteins; D058539:Phosphatidylinositol 3-Kinase; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D014315:Triterpenes; D000097245:Ursolic Acid; C526295:Irs1 protein, mouse; C495693:Slc2a4 protein, mouse
keywords: C57/BL/6J mice; Glucose transporter 4; High-fat diet; Insulin receptor; Insulin signaling; Rosiglitazone; Skeletal muscle; Ursolic acid