title: [I10W]tigerinin-1R enhances both insulin sensitivity and pancreatic beta cell function and decreases adiposity and plasma triglycerides in high-fat mice.
abstract: OBJECTIVE
  We have previously described the insulinotropic activities of [I10W]tigerinin-1R (RVCSAIPLPWCH.NH2) in vitro. In this study, we investigated the effects of the peptide on nutrient homoeostasis in mice with diet-induced obesity and insulin resistance.
  
  
  METHODS
  Male NIH Swiss mice were maintained on a high-fat diet for 12 weeks prior to the study. Twice-daily intraperitoneal injections of [I10W]tigerinin-1R (75 nmol/kg body weight) were administered for 28 days. Body weight, energy intake, body fat content, and plasma concentrations of triglyceride, cholesterol, non-fasting glucose and insulin were monitored. Effects of the peptide on glycaemic control were measured by glucose tolerance and insulin sensitivity tests. Pancreatic hormone content and insulin secretory responses of islets isolated from treated and untreated mice were examined. Immunohistochemical analysis was performed to study possible changes in islet morphology.
  
  
  RESULTS
  Administration of [I10W]tigerinin-1R to high-fat-fed mice produced significant (P < 0.05) decreases in plasma glucose, glucagon and triglyceride concentrations and an increase in plasma insulin compared to high-fat-fed controls. No changes in body weight or energy intake were observed with peptide treatment, but glycaemic control was significantly improved in response to oral or intraperitoneal glucose. Insulin sensitivity and secretory responses of islets to established insulin secretagogues were also significantly improved in peptide-treated mice. Total body fat, pancreatic insulin and glucagon contents, islet, beta and alpha cell areas were all significantly decreased in treated mice.
  
  
  CONCLUSIONS
  This study shows that [I10W]tigerinin-1R improves insulin sensitivity, islet function and glycaemic control in high-fat-fed mice and has potential as a template for development of novel anti-diabetic agents.
authors.affiliation: SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, Northern Ireland, UK.
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Srinivasan
authors.affiliation: SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, Northern Ireland, UK.
authors.forename: Opeolu O
authors.initials: OO
authors.lastname: Ojo
authors.affiliation: SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, Northern Ireland, UK.
authors.forename: Bosede O
authors.initials: BO
authors.lastname: Owolabi
authors.affiliation: SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, Northern Ireland, UK.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Conlon
authors.affiliation: SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, Northern Ireland, UK.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
authors.affiliation: SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, Northern Ireland, UK. y.abdel-wahab@ulster.ac.uk.
authors.forename: Yasser H A
authors.initials: YH
authors.lastname: Abdel-Wahab
mesh_terms: D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D059305:Diet, High-Fat / Q000009:adverse effects; D005934:Glucagon / Q000097:blood; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D009765:Obesity / Q000188:drug therapy; D010455:Peptides / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood*
chemical_list: D023181:Antimicrobial Cationic Peptides; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008055:Lipids; D010455:Peptides; D014280:Triglycerides; C469876:tigerinin 1; D005934:Glucagon
keywords: Amphibian skin peptide; Insulin release; Insulin sensitivity; Tigerinin-1R; Type 2 diabetes