Insulin and glucagon impairments in relation with islet cells morphological modifications following long term pancreatic duct ligation in the rabbit--a model of non-insulin-dependent diabetes.

Plasma levels of glucose, insulin and glucagon were measured at various time intervals after pancreatic duct ligation (PDL) in rabbits. Two hyperglycemic periods were observed: one between 15-90 days (peak at 30 days of 15.1 +/- 1.2 mmol/l, p < 0.01), and the other at 450 days (11.2 +/- 0.5 mmol/l, p < 0.02). The first hyperglycemic episode was significantly correlated with both hypoinsulinemia (41.8 +/- 8 pmol/l, r = -0.94, p < 0.01) and hyperglucagonemia (232 +/- 21 ng/l, r = 0.95, p < 0.01). However, the late hyperglycemic phase (450 days), which was not accompanied by hypoinsulinemia, was observed after the hyperglucagonemia (390 days) produced by abundant immunostained A-cells giving rise to a 3-fold increase in pancreatic glucagon stores. The insulin and glucagon responses to glucose loading at 180, 270 and 450 days reflected the insensitivity of B- and A-cells to glucose. The PDL rabbit model with chronic and severe glycemic disorders due to the predominant role of glucagon mimicked key features of the NIDDM syndrome secondary to exocrine disease.