title: Myoinositol ameliorates high-fat diet and streptozotocin-induced diabetes in rats through promoting insulin receptor signaling.
abstract: Mimosa pudica Linn. (Mimosaceae) has been traditionally used for the management of type 2 diabetes mellitus (T2DM) in India. The present study evaluates the therapeutic efficacy of myoinositol (25 and 50mg/kg) isolated from M. pudica stem methanol extract in Triton WR-1339 induced hyperlipidemic and high-fat diet (HFD) fed-streptozotocin (STZ)-induced insulin-resistant diabetic rats. Lipid biomarkers, fasting blood glucose (FBG), changes in body weight, food and water intakes, plasma insulin, HOMA-IR, oral glucose tolerance, intraperitoneal insulin tolerance, urea, creatinine, marker enzymes of liver function, β-cell function and the expression levels of insulin receptor-induced signaling molecules were studied. Molecular-docking was also carried out to determine the possible interactions of myoinositol into the active sites of insulin-induced signaling markers. In addition, histology of liver, pancreas, kidney, heart and adipose tissues were also performed. In Triton WR-1339 induced hyperlipidemic rats, myoinositol (25 and 50mg/kg) exhibited significant reductions in total cholesterol: 37.5% and 59.73%, triglycerides: 57.75% and 80.14% and LDL-c: 81.44% and 101.75% respectively. HFD fed-STZ receiving myoinositol (25 and 50mg/kg) showed significant reductions in fasting blood glucose: 55.68% and 56.48%, plasma insulin level: 25.45% and 27.06% when compared with diabetic control. It significantly normalized the hyperglycemia induced biochemical abnormalities in insulin-resistant diabetic rats. Furthermore, it demonstrated cytoprotective effects besides increase in the intensity of positive reaction for insulin in pancreas. Myoinositol enhanced the level of PPARγ expression in the adipose tissue of treated rats when compared with rats that did not receive drug treatment; also, it significantly upregulated GLUT4 and IR signaling molecules. Myoinositol had predicted the interactions within the active sites of PPARγ, GLUT4 and IR. These findings suggested that myoinositol could play an effective role in glucose disposal into adipose tissue by insulin-dependent signaling cascade mechanism; hence it could be used in the treatment of obesity-associated T2DM.
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, India.
authors.forename: Poovathumkal James
authors.initials: PJ
authors.lastname: Antony
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, India; Department of Medicine, Postgraduate Programme in Health Sciences, Federal University of Sergipe, Aracaju, Sergipe, Brazil.
authors.forename: Gopalsamy Rajiv
authors.initials: GR
authors.lastname: Gandhi
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, India.
authors.forename: Antony
authors.initials: A
authors.lastname: Stalin
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, India.
authors.forename: Kedike
authors.initials: K
authors.lastname: Balakrishna
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, India.
authors.forename: Erenius
authors.initials: E
authors.lastname: Toppo
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, India.
authors.forename: Kuppusamy
authors.initials: K
authors.lastname: Sivasankaran
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, India; International Scientific Partnership Program (ISPP), King Saud University, Riyadh, Saudi Arabia. Electronic address: eriloyola@hotmail.com.
authors.forename: Savarimuthu
authors.initials: S
authors.lastname: Ignacimuthu
authors.affiliation: Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Naif Abdullah
authors.initials: NA
authors.lastname: Al-Dhabi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D059305:Diet, High-Fat; D004327:Drinking Behavior / Q000187:drug effects; D005215:Fasting / Q000097:blood; D005247:Feeding Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005951:Glucose Tolerance Test; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy; D007150:Immunohistochemistry; D007294:Inositol / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D062105:Molecular Docking Simulation; D011092:Polyethylene Glycols; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D012333:RNA, Messenger; D011092:Polyethylene Glycols; D007294:Inositol; D011972:Receptor, Insulin; C016811:tyloxapol
keywords: Adipose; Biochemical; Diabetes; Histology; Myoinositol; β-cell