Changes of Islet Size and Islet Size Distribution Resulting from Protein‐Malnutrition in Lean (Fa/Fa) and Obese (fa/fa) Zucker Rats

Abstract

Potential alterations in islet size and islet size distribution resulting from protein malnutrition were studied in lean ( F d F u ) and obese (fuNu) Zucker rats. The purpose was to investigate whether the distribution of enlarged islets in obese rats was altered by low-protein feeding. Four-week-old, male, 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 dissected at autopsy and immunostained for insulin. Islet size and distribution were determined by morphometric analysis. Bodyweight gain, food intake, 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 controls. However, obese rats were still hyperinsulinemic compared with lean rats. Protein malnutrition resulted in a shift in distribution of islets to smaller size both in lean and in obese rats, with an increase in the population of small islets (S100 pm2) and a decrease in the population of large islets (>20,000 pm'). In lean and obese rats fed low protein, P-cell weight was significantly lower, f3 cell volume fraction tended to decrease, BRIGITTE REUSENS, CLAUDE REMACLE, JO- and islet number per section area was significantly elevated when compared with controls. Taken together, these results show that protein deficiency alters the endocrine pancreas in both lean and obese Zucker rats. Although the decrease in islet size and the shift in distribution to smaller islets most likely contribute to the decrease in serum insulin concentration, these changes appear insufficient to normalize hyperinsulinemia in the obese Zucker rat.

Reduced pancreatic β-cell mass is associated with decreased FoxO1 and Erk1/2 protein phosphorylation in low-protein malnourished rats

“…Our data also confirm previous studies (8,9) showing that rats submitted to a low-protein diet exhibit reduced β-cell mass ( Figure 1C). An increase in the population of small islets and a decrease in the population of large islets were observed by Tse et al (9), as also observed in the present study.…”

“…An increase in the population of small islets and a decrease in the population of large islets were observed by Tse et al (9), as also observed in the present study. Smaller islets can be easily observed in pancreas sections from LP rats ( Figure 1B), which were in agreement with the reduced mean islet size.…”

“…Malnourishment induces functional and structural alterations in the endocrine pancreas in fetal, neonatal (1)(2)(3)(4) and adult rats (5)(6)(7)(8)(9). We have shown that malnutrition caused by a low-protein diet increases insulin sensitivity in peripheral tissues of adult rats (6,7).…”

“…Malnourished rats exhibit reduced levels of circulating insulin that may be a consequence of decreased islet responsiveness to glucose (5)(6)(7). Reduction of islet size is also observed in these rats (6,9). Other studies have reported alterations in pancreatic islet structure in models of undernutrition.…”

Increased islet neogenesis without increased islet mass precedes autoimmune attack in diabetes-prone rats

“…6 There are also reports in other rat strains (Zucker lean and obese), that large islets are specifically decreased in animals subjected to protein malnutrition. 49 A recent study also showed decreased area of large islets in offspring of Wistar rats fed a low-protein diet. 50 Whether or not very large islets seen in BBc rats are a common feature of islet size distribution in humans remains unclear.…”