It has been reported that afferent arteriolar hyalinosis is involved in the major lesions of diabetic glomerulopathy. However, controversy has been evident with respect to the stage at which this lesion develops. In the present study, we examined the renal tissues of 40-week alloxan-diabetic rats, both light and electron microscopically, with particular attention to glomerular arteriolar changes. Additional clinical parameters, such as urine albumin excretion and creatinine clearance, were also studied. Light microscopy revealed the presence of hyalinosis of the afferent arterioles. Electron microscopy showed such arteriolar changes to represent the accumulation of basement membrane material and that smooth muscle and JG cells were decreased in number in the arteriolar lesions. Among the clinical parameters studied, urine albumin excretion and creatinine clearance were significantly higher in the diabetic rats (301±159μg/day and 59.2±6.4μl/min/100 g b. w.) than in the controls (33±25μg/day and 40.5±9.2μl/min/100 gb. w.), whereas mean blood pressure was not elevated. On the basis of these clinical data, the renal involvement of our diabetic rats corresponds to stage II of Mogensen's classification. Thus, it appears that afferent arteriolar hyalinosis occurs at a rather early stage of diabetic nephropathy in our animal model.
The effect of nicergolin, a cerebral circulation ameliorator, at a dosage of 15 mg/day for a week, on glucose metabolism, tissue, insulin sensitivity and insulin secretory responses, were investigated in seven middle-aged (48±4yr; mean±SD) non-obese healthy volunteers. The study was conducted by means of a 90 min hyperglycemic (200 mg/dl) clamp followed by a 90 min euglycemic hyperinsulinemic (95 mg/dl, 100μU/ml) clamp. The hyperglycemic clamp revealed a tendency toward increased insulin secretion in the early (5 min)(32±21.7 vs 37±33.0; ns) and late phases (60-90 min)(21+6.6 vs 23±8.3; ns) with nicergolin. The euglycemic hyperglycemic clamp demonstrated a significant increase in the average glucose uptake rate with nicergolin (10.0±1.9 vs 8.9±1.4 mg/kg. min: p< 0.05 by paired t-test). These data indicated the possibility that a cerebral circulation ameliorator such as nicergolin may improve glucose metabolism by increasing tissue glucose uptake.