title: Beneficial effects of tigerinin-1R on glucose homeostasis and beta cell function in mice with diet-induced obesity-diabetes.
abstract: OBJECTIVE
  This paper investigates the anti-diabetic effects of tigerinin-1R (RVCSAIPLPICH.NH2), a previously described amphibian host defence peptide, in mice with diet-induced obesity-diabetes.
  
  
  METHODS
  Proteolytic degradation of synthetic tigerinin-1R was investigated by reversed-phase HPLC and MALDI-TOF mass spectrometry. Changes in glycaemic responses and metabolic parameters were measured in mice with high fat diet-induced obesity-diabetes treated with twice-daily with of tigerinin-1R (75 nmol/kg bw) for 15 days. Indirect calorimetry and body composition were measured by CLAMS and DEXA whole body scanning. Insulin secretory responses of islets isolated from treated and untreated mice were examined.
  
  
  RESULTS
  Tigerinin-1R was resistant to in vitro degradation by plasma enzymes. Twice-daily injection of tigerinin-1R for 15 days had no significant effect on food intake or body weight. Non-fasting glucose levels were significantly lowered, and insulin levels were elevated compared to saline treated controls. Glycaemic responses to both oral and intraperitoneal glucose administration were significantly improved by tigerinin-1R treatment. Plasma insulin was also significantly elevated. The peptide had no significant effect on insulin sensitivity but the beta cell responses of islets isolated from treated mice to a range of nutrients and peptidergic secretagogues were significantly improved. Oxygen consumption, CO2 production, respiratory exchange ratio, energy expenditure and body composition were not significantly altered by treatment with tigerinin-1R.
  
  
  CONCLUSIONS
  Tigerinin-1R significantly improves glucose homeostasis and may have potential as a novel antidiabetic agent.
authors.affiliation: School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, UK.
authors.forename: Opeolu O
authors.initials: OO
authors.lastname: Ojo
authors.affiliation: School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, UK.
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Srinivasan
authors.affiliation: School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, UK.
authors.forename: Bosede O
authors.initials: BO
authors.lastname: Owolabi
authors.affiliation: School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, UK.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
authors.affiliation: School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, UK. Electronic address: y.abdel-wahab@ulster.ac.uk.
authors.forename: Yasser H A
authors.initials: YH
authors.lastname: Abdel-Wahab
mesh_terms: D015502:Absorptiometry, Photon; D029845:Amphibian Proteins / Q000378:metabolism / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003920:Diabetes Mellitus / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D059305:Diet, High-Fat / Q000009:adverse effects; D004734:Energy Metabolism / Q000187:drug effects; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D010101:Oxygen Consumption / Q000235:genetics; D059748:Proteolysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors
chemical_list: D029845:Amphibian Proteins; D001786:Blood Glucose; D007328:Insulin; C000593416:tigerinin-1R peptide, Hoplobatrachus rugulosus; D002245:Carbon Dioxide
keywords: Amphibian skin peptide; Insulin-release; Obesity; Tigerinin-1R; Type 2 diabetes