Tigerinin-1R: a potent, non-toxic insulin-releasing peptide isolated from the skin of the Asian frog, Hoplobatrachus rugulosus
Article first published online: 27 OCT 2011
© 2011 Blackwell Publishing Ltd
Diabetes, Obesity and Metabolism
Volume 13, Issue 12, pages 1114–1122, December 2011
How to Cite
Ojo, O. O., Abdel-Wahab, Y. H. A., Flatt, P. R., 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: 1114–1122. doi: 10.1111/j.1463-1326.2011.01470.x
- Issue published online: 27 OCT 2011
- Article first published online: 27 OCT 2011
- Accepted manuscript online: 7 JUL 2011 12:00AM EST
- Date submitted 26 May 2011; date of first decision 10 June 2011; date of final acceptance 5 July 2011
- antidiabetic drug;
- beta cell;
- dose–response relationship;
- insulin secretagogue;
- type 2 diabetes
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 β cells. Insulin-releasing potencies of synthetic peptides and their effects on membrane potential and intracellular Ca2+ 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.NH2), 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 α-amidation was necessary for high potency and a possible mechanism of action of the peptide-involved membrane depolarization and an increase in intracellular Ca2+ 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.