Correlation Between Morphology and Function in Isolated Islets of the Zucker Rat

Abstract

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 the perifusion system. Islet size was arbitrarily defined as large (greater than 0.45 mm) or small (smaller than 0.12 mm). Protein content and volume (V = 4/3pir3) 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 microU/islet/min, P less than 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 less than 0.005). In terms of islet volume, however, large islets were inefficient insulin releasers as compared to small islets (P less than 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/microgram protein per minute, P less than 0.05). Arginine produced the same effect on glucagon release (P less than 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.

Plasma glucagon responses to insulin-induced hypoglycemia and arginine in spontaneous non-insulin-dependent diabetes mellitus (NIDDM) rats, Otsuka Long Evans Tokushima Fatty (OLETF) strain

“…Similar morphological changes in the islets have been observed in male Zucker fatty rats (23), which also show a decreased response of A cells to hypoglyce¬ mia (24). As reported previously (10), exercise training prevented morphological alterations of the islets of OLETF rats of 24 weeks old, such as enlargement and lobulation of islets due to proliferation of connective tissue.…”

Attenuation of type 2 diabetes mellitus in the male Zucker diabetic fatty rat: the effects of stress and non-volitional exercise

“…Thus, it appears that moderate exercise training improves beta cell function either directly by increasing beta cell mass or as a result of bsparingQ insulin needs by increasing peripheral insulin action. Indeed, a strong positive correlation exists between the maintenance of normal islet morphology and beta cell function [50]. Our immunohistochemical analysis of the pancreas showed that in exercised animals there was a significant attenuation in the reduction of beta cell mass when compared with age-matched controls (Fig.…”

Preservation of Insulin Release Periodicity from Individual Islets of Obese Zucker Rats

“…We have previously shown that when groups of islets from obese and lean rats are perifused, the observed pattern of insulin release in response to stimulation is closely correlated to islet size (Hayek and Woodside 1979). Perifusion of groups of islets however, obscures the synchrony of insulin secretion in discreet short pulses exhibited by individual, normal islets (Beigelman, Thomas, Slavin, Shu and Bessman 1973).…”

“…Individual large islets (0.4 to 0.8 mm diameter) from obese rats were perifused in Hanks' solution adjusted to a pH of 7.4 and gassed continuously with 95 % 0 2 and 5 % C0 2 (Hayek and Woodside 1979).Flow rate, maintained at 1 ml/min, allowed the collection of 250 µl aliquots every 15 seconds. Aliquots were immediately frozen and simultaneously assayed at a later time for insulin by radioimmunoassay.…”