Premilovac_et_al-2017-Scientific_Reports.pdf (1.98 MB)
A New Method for Targeted and Sustained Induction of Type 2 Diabetes in Rodents
journal contribution
posted on 2023-05-19, 13:00 authored by Dino PremilovacDino Premilovac, Robert GasperiniRobert Gasperini, Samantha SawyerSamantha Sawyer, Adrian WestAdrian West, Michelle Keske, Bruce TaylorBruce Taylor, Lisa FoaLisa FoaType 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.
Funding
National Health & Medical Research Council
History
Publication title
Scientific ReportsVolume
7Article number
14158Number
14158Pagination
1-10ISSN
2045-2322Department/School
Tasmanian School of MedicinePublisher
Nature Publishing GroupPlace of publication
United KingdomRights statement
Copyright 2017 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/Repository Status
- Open