The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes

Abstract

Background: Diabetes in humans induces chronic complications such as cardiovascular damage, cataracts and retinopathy, nephropathy and polyneuropathy. The most common animal model of human diabetes is streptozotocin(STZ)-induced diabetes in the rat. Methods: This project has assessed cardiovascular, ocular and neuropathic changes over a period of 24 weeks post-STZ treatment in rats. Results: STZ-diabetic rats (n=96) showed stable signs of diabetes (hyperglycaemia, increased water and food intake with no increase in body weight); 52% of untreated STZ-diabetic rats (n=50) survived 24 weeks. STZ-diabetic rats were normotensive with slowly developing systolic and diastolic dysfunction and an increased ventricular stiffness. Ventricular action potential durations were markedly prolonged. STZ-diabetic rats developed stable tactile allodynia. Cataracts developed to presumed blindness at 16 weeks but proliferative retinopathy was not observed even after 24 weeks. Conclusion: The chronic STZ-diabetic rat mimics many but not all of the chronic complications observed in the diabetic human. The chronic STZ-diabetic rat may be a useful model to test therapeutic approaches for amelioration of chronic diabetic complications in humans.