PMID- 28192884 OWN - NLM STAT- MEDLINE DCOM- 20170314 LR - 20211103 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 88 DP - 2017 Apr TI - Myoinositol ameliorates high-fat diet and streptozotocin-induced diabetes in rats through promoting insulin receptor signaling. PG - 1098-1113 LID - S0753-3322(16)32486-6 [pii] LID - 10.1016/j.biopha.2017.01.170 [doi] AB - 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, beta-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 PPARgamma 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 PPARgamma, 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. CI - Copyright (c) 2017 Elsevier Masson SAS. All rights reserved. FAU - Antony, Poovathumkal James AU - Antony PJ AD - Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, India. FAU - Gandhi, Gopalsamy Rajiv AU - Gandhi GR AD - 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. FAU - Stalin, Antony AU - Stalin A AD - Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, India. FAU - Balakrishna, Kedike AU - Balakrishna K AD - Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, India. FAU - Toppo, Erenius AU - Toppo E AD - Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, India. FAU - Sivasankaran, Kuppusamy AU - Sivasankaran K AD - Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, India. FAU - Ignacimuthu, Savarimuthu AU - Ignacimuthu S AD - 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. FAU - Al-Dhabi, Naif Abdullah AU - Al-Dhabi NA AD - Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, King Saud University, Riyadh, Saudi Arabia. LA - eng PT - Journal Article DEP - 20170210 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Blood Glucose) RN - 0 (Insulin) RN - 0 (Lipids) RN - 0 (RNA, Messenger) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 4L6452S749 (Inositol) RN - EC 2.7.10.1 (Receptor, Insulin) RN - Y27PUL9H56 (tyloxapol) SB - IM MH - Administration, Oral MH - Animals MH - Blood Glucose/metabolism MH - Body Weight/drug effects MH - Diabetes Mellitus, Experimental/blood/complications/*drug therapy/pathology MH - Diet, High-Fat MH - Drinking Behavior/drug effects MH - Fasting/blood MH - Feeding Behavior/drug effects MH - Gene Expression Regulation/drug effects MH - Glucose Tolerance Test MH - Hyperlipidemias/blood/complications/drug therapy MH - Immunohistochemistry MH - Inositol/administration & dosage/chemistry/pharmacology/*therapeutic use MH - Insulin/blood MH - Insulin Resistance MH - Kidney/drug effects/pathology MH - Lipids/blood MH - Liver/drug effects/pathology MH - Male MH - Molecular Docking Simulation MH - Polyethylene Glycols MH - RNA, Messenger/genetics/metabolism MH - Rats, Wistar MH - Receptor, Insulin/*metabolism MH - *Signal Transduction/drug effects OTO - NOTNLM OT - Adipose OT - Biochemical OT - Diabetes OT - Histology OT - Myoinositol OT - beta-cell EDAT- 2017/02/15 06:00 MHDA- 2017/03/16 06:00 CRDT- 2017/02/15 06:00 PHST- 2016/11/25 00:00 [received] PHST- 2017/01/30 00:00 [revised] PHST- 2017/01/30 00:00 [accepted] PHST- 2017/02/15 06:00 [pubmed] PHST- 2017/03/16 06:00 [medline] PHST- 2017/02/15 06:00 [entrez] AID - S0753-3322(16)32486-6 [pii] AID - 10.1016/j.biopha.2017.01.170 [doi] PST - ppublish SO - Biomed Pharmacother. 2017 Apr;88:1098-1113. doi: 10.1016/j.biopha.2017.01.170. Epub 2017 Feb 10.