Obesity in the Zucker rat is accompanied by hyperlipemia, hyperinsulinism, insulin resistance, pancreatic hyperplasia, and islet hypertrophy. This study correlates the morphologic heterogeneity of isolated pancreatic islets with secretion of insulin and glucagon in a perifusion system. Islet size was arbitrarily defined as large (>0.45 mm) or small (<0.12 mm). Protein content and volume (V = 4/3πr3) were calculated for groups and individual islets, respectively. Islets from obese rats secreted more insulin in response to glucose and aminophylline than islets from lean rats (peak 7.8 ± 2.4 vs. 1.5 ± 0.37 μU/islet/min, P < 0.005). Insulin release was related directly to islet size and protein content. Small islets from lean and obese animals produced less insulin per islet than large islets (P < 0.005). In terms of islet volume, however, large islets were inefficient insulin releasers as compared to small islets (P < 0.005). Stimulation with Br-cAMP released glucagon from islets of lean but not from large islets of obese animals (peak 11 ±3.3 vs. 4.1 ± 0.3 pg/μg protein per minute, P < 0.05). Arginine produced the same effect on glucagon release (P < 0.05) as stimulation with Br-cAMP. The observed increased insulin release rates and the blunted glucagon response are related to islet size in the pancreas of the Zucker rat.

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