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Abstract

Type 2 diabetes is a chronic metabolic disorder that is becoming a leading cause of morbidity and mortality. The prolonged time-course of human type 2 diabetes makes modelling of the disease difficult and additional animal models and methodologies are needed. The goal of this study was to develop and characterise a new method that allows controlled, targeted and sustained induction of discrete stages of type 2 diabetes in rodents. Using adult, male rats, we employed a three-week high fat-diet regimen and confirmed development of obesity-associated glucose intolerance, a key feature of human type 2 diabetes. Next, we utilised osmotic mini-pumps to infuse streptozotocin (STZ; doses ranging 80–200 mg/kg) over the course of 14-days to decrease insulin-producing capacity thus promoting hyperglycemia. Using this new approach, we demonstrate a dose-dependent effect of STZ on circulating glucose and insulin levels as well as glucose tolerance, while retaining a state of obesity. Importantly, we found that insulin secretion in response to a glucose load was present, but reduced in a dose-dependent manner by increasing STZ. In conclusion, we demonstrate a novel method that enables induction of discrete stages of type 2 diabetes in rodents that closely mirrors the different stages of type 2 diabetes in humans.

Item Type:	Article
Authors/Creators:	Premilovac, D and Gasperini, RJ and Sawyer, S and West, A and Keske, M and Taylor, BV and Foa, L
Keywords:	diabetes, hyperglycaemia, diabetic model
Journal or Publication Title:	Scientific Reports
Publisher:	Nature Publishing Group
ISSN:	2045-2322
DOI / ID Number:	10.1038/s41598-017-14114-4
Copyright Information:	Copyright 2017 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
Related URLs:	Google Scholar: Premilovac, D UTAS Profile: Premilovac, D UTAS Profile: Gasperini, RJ UTAS Profile: Keske, M UTAS Profile: Taylor, BV Google Scholar: Foa, L UTAS Profile: Foa, L
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