Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2016

Osmotic mini-pump delivered streptozotocin allows targeted and consistent induction of type 2 diabetes in rats. (#69)

Dino Premilovac 1 , Robert Gasperini 1 , Bruce Taylor 2 , Michelle Keske 2 , Lisa Foa 1
  1. School of Medicine, University of Tasmania, Hobart, TAS, Australia
  2. Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia

Modelling T2D accurately in the laboratory without the use of genetic models has proven difficult. The most commonly used T2D rat model is the high-fat-fed (HFD) plus streptozotocin (STZ) injected model. Thus far, studies have utilised either intraperitoneal or intravenous injections of STZ to reduce β-cell number and function. However, the extent of β-cell death using injection methods is exceedingly difficult to control/predict between animals due to single-pass effect of STZ on β-cells. We sought to identify a novel mode of administering STZ to consistently and reproducibly induce T2D. Male Sprague-Dawley rats were maintained on HFD (40% energy from fat) for three weeks, then treated with STZ for an additional 2 weeks. STZ was prepared in citrate buffered saline (pH4.4) and 2ml total volume was loaded into osmotic mini-pumps (2ML2). Mini-pumps were implanted subcutaneously and delivery of STZ occurred at a constant rate of 5µl/hr for 14 days. Intraperitoneal glucose tolerance tests (GTT; 1g/kg) were conducted at baseline (Day0), after HFD (Day20), and after HFD+STZ (Day35) to measure the degree of insulin resistance/glucose tolerance (Figure1). Osmotic mini-pump delivered STZ caused a dose-dependent and reproducible increase in glucose intolerance (Figure1). Thus, HFD and osmotic mini-pump delivered STZ allows for titratable induction of T2D in rats. This is a powerful methodological advance that will allow researchers to more accurately investigate the suite of diabetic complications which arise at different time-points in the T2D continuum.


Figure 1. Osmotic mini-pump delivered STZ dose-dependently worsens glucose tolerance . Glucose tolerance tests (1g/kg) were performed after an overnight fast. Area under the glucose curve (AUC) was calculated for each test. Data are means±SEM for n=6 animals in each group. *Denotes significance (p<0.05) versus day0 within group; #denotes significance (p<0.05) versus day20 within group; ‡denotes significance (p<0.05) versus preceding dose at day35. Low=100mg/kg; Med=110mg/kg; High=120mg/kg; V.High=150mg/kg; Extreme=200mg/kg.