Controlled induction of type 2 diabetes in mice using high fat diet and osmotic-mini pump infused streptozotocin.
Study Goal
The researchers aimed to develop and characterize a reproducible, non-transgenic mouse model of sustained type 2 diabetes (T2D) using a high-fat diet (HFD) combined with streptozotocin (STZ) infusion.
Results Summary
The study found that combining HFD with STZ (200 mg/kg) led to increased blood glucose, impaired glucose tolerance, obesity, and hepatic dyslipidaemia, while maintaining reduced but detectable insulin production without overt beta cell loss. The model replicated key pathophysiological changes seen in human T2D.
Population
Adult male C57BL/6 mice
Effective Dosage
High-fat diet (unspecified composition) for 17 weeks; STZ (200-350 mg/kg) infused over 14 days
Duration
17 weeks (HFD) + 12 weeks post-STZ monitoring
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
high-fat diet (HFD) for 17 weeks | increase | obesity and hepatic dyslipidaemia | Adult, male C57BL/6 mice | - | leads to | #1 |
combination of HFD and 200 mg/kg STZ delivered by mini-pump | increase | increased blood glucose concentrations | Adult, male C57BL/6 mice | - | leads to | #2 |
combination of HFD and 200 mg/kg STZ delivered by mini-pump | decrease | impaired glucose tolerance | Adult, male C57BL/6 mice | - | leads to | #3 |
STZ treatment | decrease | plasma insulin concentration | Adult, male C57BL/6 mice | - | showed that | #4 |
STZ treatment | no change | overt loss of beta cell mass | Adult, male C57BL/6 mice | - | show that there is | #5 |
Type 2 diabetes (T2D) is a progressive metabolic disorder characterised by obesity, insulin resistance, impaired glucose tolerance, and hyperglycaemia. The long time-course of T2D in humans makes accurate modelling of sustained T2D in animal models difficult. The goal of this study was to develop and characterise an accurate and reproducible, non-transgenic model of sustained T2D in mice. Adult, male C57BL/6 mice were placed on a high-fat diet (HFD) for 17 weeks. From weeks 3-5, osmotic mini-pumps were implanted subcutaneously to slowly infuse streptozotocin (STZ; 200-350 mg/kg) for 14-days after which mini-pumps were removed. Body weight, blood glucose concentration, and glucose tolerance were monitored for 12 weeks post STZ treatment. Our data demonstrate that the combination of HFD and 200 mg/kg STZ delivered by mini-pump leads to increased blood glucose concentrations and impaired glucose tolerance, while maintaining obesity and hepatic dyslipidaemia. In week 17, plasma insulin concentration was assessed and showed that with STZ treatment, mice still produce insulin, but that this is reduced compared with mice on HFD only. Lastly, we examined pancreas sections using immunohistochemistry and show that there is no overt loss of beta cell mass. In conclusion, we demonstrate development of a reproducible in vivo model of T2D in mice that replicates a number of key pathophysiological changes seen in humans with T2D.