Animal Models of Diabetic Uropathy

Purpose

Diabetes mellitus is a group of debilitating and costly diseases with multiple serious complications. Lower urinary tract complications or diabetic uropathy are among the most common complications of diabetes mellitus, surpassing widely recognized complications such as neuropathy and nephropathy. Diabetic uropathy develops in individuals with types 1 and 2 diabetes, and little is known about the natural history of these common and troublesome complications. Animal models have the potential to reveal mechanisms and aid in the development of treatment strategies.

Materials and Methods

We present a review of available animal models of diabetes mellitus relative to their use in the study of diabetic uropathy.

Results

Large and small animal models of diabetes mellitus are available. While large animals such as dogs and swine may closely mirror the human disease in size and phenotype, the time between diabetic complication onset and development, and associated husbandry expenditures can make acquiring data on statistically valid sample sizes prohibitively expensive. In contrast, small animal models (rats and mice) have much lower expenditures for a larger number of animals and compressed observation time due to a shorter life span. Also, mice are readily manipulated genetically to facilitate the isolation of the effect of single genes (transgenic and knockout mice). Type 1 diabetes mellitus can be induced chemically with streptozotocin, which is selectively toxic to pancreatic β cells. Type 2 diabetes mellitus models have been developed by selective breeding for hyperglycemia with or without associated obesity. Diabetic uropathy has been noted in several well characterized, predictable animal models of diabetes mellitus.

Conclusions

Diabetic uropathy, including diabetic bladder dysfunction, has been more frequently studied in small animals with type I diabetes. The recent availability of transgenic models provides a new opportunity for further studies of diabetic uropathy in mouse models of types I and II diabetes mellitus.

Key Words: urinary bladder, diabetes mellitus, type I, diabetes mellitus, type II, diabetic complications, models, animal

Abbreviations and Acronyms: BMI, body mass index, DBD, diabetic bladder dysfunction, DM, diabetes mellitus, DU, diabetic uropathy, NON, Non Obese Non Diabetic, NZO, New Zealand Obese, STZ, streptozotocin, T1D, type I DM, T2D, type II DM, UI, urinary incontinence, ZDF, Zucker diabetic fatty