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A New Method for Targeted and Sustained Induction of Type 2 Diabetes in Rodents
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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 |
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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/ |
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