Wistar fatty rat, which has been established by transferring the fa gene of Zucker fatty rat to the Wistar Kyoto rat, has many features in common with human
NIDDM. It exhibits hyperglycemic
obesity with
hyperinsulinemia and
insulin resistance. It is unclear, however, whether a defect in the beta-cell proliferation is related to the onset of
diabetes mellitus together with
insulin resistance in this model rat. To determine this, we compared non-fasting plasma
glucose levels,
insulin content and beta-cell mass in the remnant pancreas of Wistar fatty rats with those in their diabetic-resistant lean counterparts after a 70% partial
pancreatectomy. We also examined whether such a defect, if present, could be improved by either
phlorizin or
nicotinamide. We further investigated if there were any differences in these parameters between the phenotypically identical but genotypically different Wistar lean rats with a gene type of homogeneous Fa/Fa and that of heterogeneous Fa/fa. Male rats, 6 weeks of age, were allocated at random into two groups: 70%
pancreatectomy (Px) and
sham-
pancreatectomy (
sham). A sustained
hyperglycemia was evident in the Px Wistar fatty rats after surgery, which was accompanied by a reduction of
insulin content and beta-cell mass in the remnant pancreas. The changes in
insulin content and beta-cell mass were unaffected by restoration of normoglycemia, induced by
phlorizin injection. The administration of
nicotinamide partially ameliorated the sustained
hyperglycemia by a slight but not significant increase in beta-cell mass. No discernible difference in the above parameters was observed between the Wistar lean rats with Fa/Fa and those with Fa/fa. These findings suggest that Wistar fatty rats have a poor capacity for proliferation of pancreatic beta-cells, which causes the onset of overt diabetes along with
insulin resistance due to extreme
obesity.