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Glucoregulatory, endocrine and morphological effects of [P5K]hymenochirin-1B in mice with diet-induced glucose intolerance and insulin resistance.

Owolabi, BO, Ojo, OO, Srinivasan, DK, Conlon, JM, Flatt, Peter and Abdel-Wahab, Yasser (2016) Glucoregulatory, endocrine and morphological effects of [P5K]hymenochirin-1B in mice with diet-induced glucose intolerance and insulin resistance. Naunyn-Schmiedeberg's Archives of Pharmacology, 389 . pp. 769-781. [Journal article]

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DOI: 10.1007/s00210-016-1243-5

Abstract

The frog skin host-defence peptide hymenochirin-1B has been shown to stimulate insulin release in vitro from isolated pancreatic islets and BRIN-BD11 clonal β-cells. This study examines the effects of 28-day administration of a more potent analogue [P5K]hymenochirin-1B ([P5K]hym-1B) (75 nmol·kg-1 body weight) to high-fat-fed mice with obesity, glucose intolerance and insulin resistance. Treatment with [P5K]hym-1B significantly decreased plasma glucose concentrations and improved glucose tolerance, insulin secretion, insulin sensitivity and increased the magnitude of the incretin effect (difference in response to oral vs intraperitoneal glucose loads). Responses to established insulin secretagogues were greater in islets isolated from treated animals compared with saline-treated controls. [P5K]hym-1B administration significantly decreased total islet area and β- and α-cell areas, and resulted in lower concentrations of circulating triglycerides and plasma and pancreatic glucagon. Peptide treatment had no effect on food intake, body weight, indirect calorimetry or circulating concentrations of amylase and marker enzymes of liver and kidney function. RT-PCR demonstrated that the Insr (insulin receptor) gene and genes involved in insulin signalling (Slc2a4, Irs1, Pik3ca, Akt1 and Pkd1) were significantly up-regulated in skeletal muscle from animals treated with [P5K]hym-1B. Expression of the Glp1r (GLP-1 receptor) and Gipr (GIP receptor) genes was significantly elevated in islets from peptide-treated mice. These data suggest that [P5K]hym-1B shows potential for development into an agent for treating patients with type 2 diabetes.

Item Type:Journal article
Keywords:Hymenochrin-1B – Type 2 diabetes – Insulin resistance – Glucose tolerance – Insulin secretion
Faculties and Schools:Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:34507
Deposited By: Dr Nigel Irwin
Deposited On:26 Apr 2016 09:25
Last Modified:26 Jul 2017 13:43

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