Figure 1.To determine the effects of hyperglycemia on insulin secretion the 90% partial pancreatectomized rat model has been studied. In this model significant hyperglycemia occurs by 2 weeks. The insulin secretory responses were assessed at 6 weeks by a glucose infusion designed to maintain a constant level of hyperglycemia after fasting (~216 mg/dl, 12 mmol/L) and both first phase (first 10 min) and second phase ( 10-60 min) responses were expressed as the mean increment in insulin concentration above basal. The drug phlorizin, administered from 2-6 weeks, normalized plasma glucose in the partially-pancreatectomized diabetic (PPD) rats [fed plasma glucose (mg/dl), control 143 ± 2, PPD 284 ± 13, Phlorizin-treated PPD (142 ± 6]. In panel A, it is noted that insulin secretion in absolute terms was markedly decreased in PPD and phlorizin-treated PPD rats. However, Panel B demonstrates that when corrected for residual pancreatic mass, maintenance of normoglycemia with phlorizin prevented the impairment in insulin secretion indicating β-cell “glucose toxicityâ€. (Adapted with permission from ref. 16).