[I10W]tigerinin-1R enhances both insulin sensitivity and pancreatic beta cell function and decreases adiposity and plasma triglycerides in high-fat mice

DK Srinivasan, OO Ojo, BO Owolabi, JM Conlon, Peter Flatt, Yasser Abdel-Wahab

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Abstract

AIMS: 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.
LanguageEnglish
Pages303-315
JournalActa Diabetologica
Volume53
Issue number2
DOIs
Publication statusPublished - 30 Mar 2016

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Adiposity
Insulin-Secreting Cells
Insulin Resistance
Triglycerides
Fats
Insulin
Glucose
Peptides
Energy Intake
Glucagon
Adipose Tissue
Body Weight
Pancreatic Hormones
Body Weight Changes
High Fat Diet
Intraperitoneal Injections
Homeostasis
Obesity
Cholesterol
Diet

Keywords

  • Tigerinin-1R – Amphibian skin peptide – Type 2 diabetes – Insulin sensitivity – Insulin release

Cite this

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title = "[I10W]tigerinin-1R enhances both insulin sensitivity and pancreatic beta cell function and decreases adiposity and plasma triglycerides in high-fat mice",
abstract = "AIMS: 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.",
keywords = "Tigerinin-1R – Amphibian skin peptide – Type 2 diabetes – Insulin sensitivity – Insulin release",
author = "DK Srinivasan and OO Ojo and BO Owolabi and JM Conlon and Peter Flatt and Yasser Abdel-Wahab",
year = "2016",
month = "3",
day = "30",
doi = "10.1007/s00592-015-0783-3",
language = "English",
volume = "53",
pages = "303--315",
journal = "Acta Diabetologica",
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TY - JOUR

T1 - [I10W]tigerinin-1R enhances both insulin sensitivity and pancreatic beta cell function and decreases adiposity and plasma triglycerides in high-fat mice

AU - Srinivasan, DK

AU - Ojo, OO

AU - Owolabi, BO

AU - Conlon, JM

AU - Flatt, Peter

AU - Abdel-Wahab, Yasser

PY - 2016/3/30

Y1 - 2016/3/30

N2 - AIMS: 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.

AB - AIMS: 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.

KW - Tigerinin-1R – Amphibian skin peptide – Type 2 diabetes – Insulin sensitivity – Insulin release

U2 - 10.1007/s00592-015-0783-3

DO - 10.1007/s00592-015-0783-3

M3 - Article

VL - 53

SP - 303

EP - 315

JO - Acta Diabetologica

T2 - Acta Diabetologica

JF - Acta Diabetologica

SN - 0940-5429

IS - 2

ER -