Interaction between high -fat diet, adrenalectomy and/or exercise on pancreatic B-cell function in obese Zucker (fa/fa) rats

Young adult obese fa/fa Zucker rats are hyperinsulinemic, hyperlipidemic and insulin resistant. Pancreatic islets of fa/fa rats exhibit increased glucose sensitivity (half maximal effective glucose concentration EC50), glucokinase sensitivity (Km) and lack of mannoheptulose (MH) inhibitory action on glucose stimulated insulin secretion (GSIS). These defects are normalized by adrenalectomy (ADX) in rat chow fed rats within 2 weeks of surgery. The current study was carried out to test the hypothesis that feeding ADX rats a high fat diet would inhibit the effects of ADX on the pancreatic islet B-cells in fa/fa rats and induce adaptive changes in the lean rats.

In pancreatic islets isolated from rat chow fed fa/fa rats, ADX significantly reduced glucokinase Km and glucose phosphorylating rate (V max) compared to those of sham rats.

The MH inhibitory response was restored by ADX in fa/fa rat islets. Pancreatic triglyceride and insulin content were higher in fa/fa rat islets than in the lean rat islets and were not affected by ADX.

Feeding a high fat diet to ADX fa/fa rats significantly increased glucokinase Vmax. The restored MH inhibitory action by ADX in fa/fa rat islets was reduced by increased dietary fat. From this study it is concluded that feeding ADX a high fat diet modulated but did not eliminate ADX action on pancreatic B-cell function in fa/fa rats.

A second study was carried out to test the hypothesis that exercise would have similar effects on pancreatic B-cell function of fa/fa rats as those induced by ADX, the rationale being that both ADX and exercise increase the sympathetic nervous system activity in the peripheral tissues including the endocrine pancreas.

Exercise significantly reduced both hexokinase Km and V max in low fat fed fa/fa rats. In low fat fed lean rats, exercise reduced glucokinase and hexokinase Km without affecting the Vmax.

Feeding a high fat diet to exercised fa/fa rats significantly increased glucokinase Km and reduced both hexokinase Km and V max. The MH response was partially restored in islets isolated from high fat exercised fa/fa rats.

In sedentary lean rats, high fat diet decreased glucokinase Km, increased pancreatic islet insulin content and FFA oxidation at the lower glucose concentration.

From these studies it is concluded that ADX is more effective than exercise in preventing pancreatic islet dysfunction in obese rats due to the induction of bigger changes in glucokinase activity and islet FFA oxidation. High fat diet was able to block some of the effects of ADX and exercise. (Abstract shortened by UMI.).