Insulin treatment improves relative hypersecretion of amylin to insulin in rats with non-insulin-dependent diabetes mellitus induced by neonatal streptozocin injection

Abstract

The dissociated release of insulin and amylin in the hyperglycemic state has been reported. This relative hypersecretion of amylin is thought to provide an important insight into how amylin aggregates to form islet amyloid deposits in non-insulin-dependent diabetes mellitus (NIDDM). The aim of the present study was to characterize the alterations of amylin hypersecretion in NIDDM with exacerbation or amelioration of diabetic control. For this purpose, neonatally streptozocin (nSTZ) diabetic rats were treated with dexamethasone (0.25 mg/kg) or Lente insulin (3 to 5 U/kg) daily for 14 days, and responses of amylin and insulin to 16.7 mmol/L glucose or 10 mmol/L arginine were evaluated in vitro using an isolated perfused pancreas system. nSTZ rats exhibited moderate elevations of plasma glucose compared with normal rats. In the isolated perfused pancreas, the molar ratio of secreted amylin to insulin in response to 16.7 mmol/L glucose by nSTZ pancreas (1.8% ± 0.2%) was significantly greater than that of normal rat pancreas (1.2% ± 0.1%). Plasma glucose levels in nSTZ rats (7.3 ± 0.4 mmol/L) increased with dexamethasone treatment (17.8 ± 1.1 mmol/L, P < .005) and decreased with insulin treatment (5.8 ± 0.4 mmol/L, P < .05). The secreted amylin to insulin ratio in dexamethasone-treated nSTZ rats was significantly greater than that of the controls ( P < .05). Moreover, insulin-treated nSTZ rats exhibited decreased amylin to insulin molar ratios compared with saline-treated nSTZ rats ( P < .05), which had the same levels as normal rats. We concluded that the relative hypersecretion of amylin in NIDDM model rats, which was exacerbated in the state of severe hyperglycemia, could be improved by near-normoglycemia achieved with insulin treatment. These findings imply the possibility that improvement of glycemic control in NIDDM may prevent increased amylin production independently of that of insulin.