Glucose-induced insulin mRNA accumulation is impaired in islets from neonatal streptozotocin-treated rats

According to the "glucose toxicity" hypothesis, hyperglycemia contributes t o defective beta-cell function in type 2, non-insulin-dependent diabetes me llitus, This concept is supported by substantial data in rodent models of d iabetes. However, the ability of glucose to stimulate the accumulation of i nsulin mRNA, a critical feature of normal beta-cell physiology, has not bee n investigated in in vivo models with chronic hyperglycemia. The aim of thi s study was to determine whether glucose-induced insulin mRNA accumulation is impaired in the neonatal streptozotocin-treated rat (n0-STZ rat), a mode l of non-obese, non-insulin-dependent diabetes mellitus. Islets of Langerha ns isolated from n0-STZ and control rats were cultured for 24 h in the pres ence of 2.8 or 16.7 mmol/l glucose, and insulin mRNA levels were measured b y Northern analysis, Insulin mRNA levels were increased more than twofold b y glucose in control islets. In contrast, no significant effect of glucose was found on insulin mRNA levels in n0-STZ islets. We conclude that insulin gene regulation by glucose is impaired in n0-STZ rat islets.