REDUCTION OF INSULIN AND TRIGLYCERIDES DELAYS GLOMERULOSCLEROSIS IN OBESE ZUCKER RATS

To evaluate the effect of insulin and/or triglycerides on the pathogen esis of glomerulosclerosis, acarbose (BAYg5421), an inhibitor of intes tinal alpha-glucosidases, was administered as a dietary admix (40 mg/1 00 g chow) to Zucker obese rats (ZOA), from 1.5 months until sacrifice at 1.5, 5, 8, 10 and 15 months. Obese (ZO) and lean (ZL) rats served as controls. Despite a similar food intake, ZOA weighed less than ZO a t all ages. Acarbose reduced serum triglycerides at all ages, and insu lin until 10 months. Glycemia remained normal in all groups. Proteinur ia developed with age and to a greater degree in ZO than in ZOA rats. In ZL, a faint proteinuria appeared only in the oldest animals. Glomer ulosclerosis, tubular and interstitial lesions rapidly affected ZO kid neys. These lesions were reduced in ZOA until 10 months. Acarbose did not modify the hypertrophy of the glomeruli that developed after three months, but slowed down the expansion of the mesangial domain seen in ZO. Thus, by reducing the amount of ingested glucose, acarbose yielde d a normal glycemia with a lesser production of insulin and reduced re nal impairment. Therefore, insulin could be a key factor involved in t he pathogenesis of glomerulosclerosis, either directly or through a co ntrol of triglyceride concentrations.