CHANGES OF ISLET SIZE AND ISLET SIZE DISTRIBUTION RESULTING FROM PROTEIN-MALNUTRITION IN LEAN (FA FA) AND OBESE (FA/FA) ZUCKER RATS/

Potential alterations in islet size and islet size distribution result ing from protein malnutrition were studied in lean (Fa/Fa) and obese ( fa/fa) Zucker rats. The purpose was to investigate whether the distrib ution of enlarged islets in obese rats was altered by low-protein feed ing. Four-week-old, mate, lean and obese Zucker rats were fed either a diet containing 20% (w/w) protein (control diet) or a diet containing 5% (w/w) protein (low-protein diet) for 3 weeks. Pancreata were disse cted at autopsy and immunostained for insulin. Islet size and distribu tion were determined by morphometric analysis. Bodyweight gain, food i ntake, and serum insulin and glucose were also measured. After 3 weeks on the diets, serum insulin was significantly lower in both lean (-75 %) and obese (-54%) rats fed low protein compared with that in control s. However, obese rats were still hyperinsulinemic compared with lean rats. Protein malnutrition resulted in a shift in distribution of isle ts to smaller size both in lean and in obese rats, with an increase in the population of smalt islets (less than or equal to 100 mu m(2)) an d a decrease in the population of large islets (>20,000 mu m(2)). In l ean and obese rats fed low protein, beta-cell weight was significantly lower, beta cell volume fraction tended to decrease, and islet number per section area was significantly elevated when compared with contro ls. Taken together, these results show that protein deficiency alters the endocrine pancreas in both lean and obese Zucker rats. Although th e decrease in islet size and the shift in distribution to smaller isle ts most likely contribute to the decrease in serum insulin concentrati on, these changes appear insufficient to normalize hyperinsulinemia in the obese Zucker rat.