Preclinical rodent models that manifest type 2 diatetes mellitus using either streptozotocin (DMIS) or alloxan (DMIA) have been well established. Both DMIS and DMIA models have served as key experimental tools to evaluate and understand the pharmacokinetic disposition of scores of drugs and therefore some key questions with respect to absorption, metabolism or elimination of drugs can be answered during the development of full-blown diabetes in the animal models. The choice of the right preclinical rodent model and adaptation of the appropriate experimental design could help to generate data to enable go or no-go decision on the clinical candidate. Also, such models may help to understand the risk potential from a drug-drug interaction perspective. The review provides an overview of the strategies and perspectives of institutionalizing DMIS and/or DMIA rat models using relevant case studies.

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The purpose of this study was to determine the use of continuous intraperitoneal insulin infusion over an extended period (in maintaining metabolic control) and to evaluate the benefits of this treatment in reversing the kidney pathology of a chronic diabetic dog with membranous glomerulopathy. Hyperglycemia was eliminated, but reevaluations of the insulin infusion pattern were necessary. An initial kidney biopsy revealed fusion of the foot processes, thickening of the basement membrane, and subendothelial deposition. After 5 months of infusion, there was less fusion of the foot processes and a decrease in the subendothelial deposition. Urinary protein loss decreased from 17.3 g/day to 625 mg/day after 2 months of infusion. The dog gained weight, muscle wasting was reversed, and his stamina returned while on continuous insulin infusion. The reduction of a life-threatening urinary protein loss to a tolerable level and the improvement in the microscopic kidney lesions observed indicate that this treatment with insulin infusion may be beneficial in the management of long-term diabetic dogs, affected with advanced kidney lesions secondary to diabetes.