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

O. O. Ojo, Yasser Abdel-Wahab, Peter Flatt, M. Mechkarska, J. M. Conlon

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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.
LanguageEnglish
Pages1114-1122
JournalDiabetes Obesity and Metabolism
Volume13
Issue number12
DOIs
Publication statusPublished - Dec 2011

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Anura
Insulin
Skin
Peptides
Glucose
High Fat Diet
L-Lactate Dehydrogenase
Membrane Potentials
Type 2 Diabetes Mellitus
Insulin Resistance
Obesity
Fats
High Pressure Liquid Chromatography
Body Weight
Membranes
Enzymes

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@article{d66f01602297424f9a4329cda2d97045,
title = "Tigerinin-1R: a potent, non-toxic insulin-releasing peptide isolated from the skin of the Asian frog, Hoplobatrachus rugulosus",
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.",
author = "Ojo, {O. O.} and Yasser Abdel-Wahab and Peter Flatt and M. Mechkarska and Conlon, {J. M.}",
year = "2011",
month = "12",
doi = "10.1111/j.1463-1326.2011.01470.x",
language = "English",
volume = "13",
pages = "1114--1122",
journal = "Diabetes, Obesity and Metabolism",
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}

TY - JOUR

T1 - Tigerinin-1R: a potent, non-toxic insulin-releasing peptide isolated from the skin of the Asian frog, Hoplobatrachus rugulosus

AU - Ojo, O. O.

AU - Abdel-Wahab, Yasser

AU - Flatt, Peter

AU - Mechkarska, M.

AU - Conlon, J. M.

PY - 2011/12

Y1 - 2011/12

N2 - 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.

AB - 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.

U2 - 10.1111/j.1463-1326.2011.01470.x

DO - 10.1111/j.1463-1326.2011.01470.x

M3 - Article

VL - 13

SP - 1114

EP - 1122

JO - Diabetes, Obesity and Metabolism

T2 - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1463-1326

IS - 12

ER -