EFFECT OF LONG-TERM TREATMENT WITH INSULIN AND OR ACARBOSE ON GLOMERULAR-BASEMENT-MEMBRANE THICKENING IN ALLOXAN-DIABETIC RATS/

Acarbose is a competitive inhibitor of the intestinal alpha-glycosidas es, that can delay absorption of intestinal carbohydrates causing thei r malabsorption. In the present paper we studied the effects of insuli n, acarbose and their association on glomerular basement membrane thic kening in alloxan-diabetic rats. Twenty-five male and female Wistar ra ts, approximately 3 months old at the beginning of the experiment, wer e assigned randomly to each of five experimental groups: normal contro l rats, alloxan-diabetic control rats, alloxan-diabetic rats treated w ith acarbose, alloxan-diabetic rats treated with insulin, and alloxan- diabetic rats treated with insulin plus acarbose. Alloxan was administ ered in a single iv dose of 42 mg/kg body weight. Insulin was given su bcutaneously at doses of 18 to 30 IU/kg corrected daily on the basis o f glycosuria and ketonuria. Acarbose was given mixed with rat chow in a dose of 50 mg/100 g chow. Body weight, water and food intake and diu resis, as well as blood and urine glucose were determined after 1, 3, 6, 9, and 12 months of treatment. Glomerular basement membrane (GBM) t hickening was determined by electron microscopy at the same times. Cle ar clinical and laboratory signs of severe diabetes, with blood glucos e levels above 200 mg/dl and urine glucose above 3000 mg/dl, were obse rved in all alloxan-diabetic control rats, in all periods of follow-up , whereas administration of insulin or acarbose reduced the blood gluc ose levels of treated groups. The most satisfactory control of blood a nd urine glucose was observed in animals treated with both insulin and acarbose. However, diarrhea was observed in diabetic rats treated wit h acarbose associated or not with insulin. GBM thickening was correlat ed with age in all groups. Beginning at six months after diabetes indu ction, the GBM of untreated diabetic rats was significantly thicker (m ean +/- SEM, 4.446 +/- 0.45 mm) than that of normal rats (2.977 +/- 0. 63 mm). Both insulin and acarbose prevented GBM thickening and their c ombination induced thickening similar to the age-dependent thickening observed for normal rats of the same age. We conclude that acarbose wh en combined with insulin may be a good option in the control of diabet es and its renal complications.