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Tigerinin-1R: a potent, non-toxic insulin-releasing peptide isolated from the skin of the Asian frog, Hoplobatrachus rugulosus

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Ojo, O. O., Abdel-Wahab, Yasser, Flatt, Peter, Mechkarska, M. and Conlon, J. M. (2011) Tigerinin-1R: a potent, non-toxic insulin-releasing peptide isolated from the skin of the Asian frog, Hoplobatrachus rugulosus. DIABETES OBESITY and METABOLISM, 13 (12). pp. 1114-1122. [Journal article]

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DOI: 10.1111/j.1463-1326.2011.01470.x

Abstract

Aim: Characterization of peptides in the skin of the Vietnamese common lowland frog Hoplobatrachus rugulosus with the ability to stimulate insulin release in vitro and improve glucose tolerance in vivo. Methods: Peptides in an extract of skin were purified by reversed-phase HPLC, and their abilities to stimulate the release of insulin and the cytosolic enzyme lactate dehydrogenase were determined using BRIN-BD11 clonal beta cells. Insulin-releasing potencies of synthetic peptides and their effects on membrane potential and intracellular Ca(2+) concentration were also measured using BRIN-BD11 cells. Effects on glucose tolerance and insulin release in vivo were determined in mice fed a high-fat diet to induce obesity and insulin resistance. Results: A cyclic dodecapeptide (RVCSAIPLPICH.NH(2)), termed tigerinin-1R, was isolated from the skin extract that lacked short-term cytotoxic and haemolytic activity but significantly (p < 0.01) stimulated the rate of release of insulin from BRIN-BD11 cells at concentrations = 0.1 nM. The maximum response was 405% of the basal rate at 5.6 mM ambient glucose concentration and 290% of basal rate at 16.7 mM glucose. C-terminal a-amidation was necessary for high potency and a possible mechanism of action of the peptide-involved membrane depolarization and an increase in intracellular Ca(2+) concentration. Administration of tigerinin-1R (75 nmol/kg body weight) to high fat-fed mice significantly (p < 0.05) enhanced insulin release and improved glucose tolerance during the 60-min period following an intraperitoneal glucose load. Conclusion: Tigerinin-1R is a potent, non-toxic insulin-releasing peptide that shows potential for development into an agent for the treatment of type 2 diabetes.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:21614
Deposited By:Dr Nigel Irwin
Deposited On:28 Mar 2012 16:08
Last Modified:28 Mar 2012 16:08

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