keske-newmethodfortargeted-2017.pdf (1.91 MB)
A new method for targeted and sustained induction of type 2 diabetes in rodents
journal contribution
posted on 2017-10-26, 00:00 authored by D Premilovac, R J Gasperini, S Sawyer, A West, Michelle KeskeMichelle Keske, B V Taylor, L 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.
History
Journal
Scientific reportsVolume
7Article number
14158Pagination
1 - 10Publisher
Nature Publishing GroupLocation
London, Eng.Publisher DOI
Link to full text
eISSN
2045-2322Language
engPublication classification
C Journal article; C1 Refereed article in a scholarly journalCopyright notice
2017, The AuthorsUsage metrics
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