Otsuka-Long-Evans-Tokushima Fatty (OLETF) rat, a genetic model of spontaneous development of NIDDM, exhibits hyperglycemic obesity with hyperinsulinemia and insulin resistance similar to that in humans. It is still unclear whether a defect in the β-cell proliferation per se is the primary pathogenetic event in OLETF rat. To determine whether it is, we used partially pancreatectomized rats as a model, with administration of phlorizin to control blood glucose level, to examine whether the capacity for proliferation of P-cells during hyperglycemia or normoglycemia differs between OLETF and their diabetes-resistant counterparts, Long-Evans-Tokushima-Otsuka (LETO) rats. We also examined whether such a defect, if present, could be improved by nicotinamide. Male rats, 6 weeks of age, were allocated at random'to two groups: 70% pancreatectomy (Px) and sham-pancreatectomy (sham). Each group was divided into four subgroups by date of killing after surgery: 3-day, 7-day, 28-day (treated with phlorizin, nicotinamide, or saline), and 91-day. A sustained hyperglycemia was evident in the Px OLETF rats after surgery, which was associated with insufficient proliferation of β-cells, characterized by decrease in β-cell labeling index in proportion to decrease in β-cell mass and reduction in insulin content in the remnant pancreas. This defect was unaffected by restoration of normoglycemia induced by phlorizin injection. Administration of nicotinamide, however, ameliorated the sustained hyperglycemia by increasing (J-ceU proliferation. These findings suggest that OLETF rats have poor capacity for proliferation of pancreatic β-cells and that this change may be the critical pathogenetic event before the onset of overt diabetes.
Poor Capacity for Proliferation of Pancreatic β-Cells in Otsuka-Long-Evans-Tokushima Fatty Rat: A Model of Spontaneous NIDDM
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Min Zhu, Yoshihiko Noma, Kenji Shima, Akira Mizuno, Toshiaki Sano; Poor Capacity for Proliferation of Pancreatic β-Cells in Otsuka-Long-Evans-Tokushima Fatty Rat: A Model of Spontaneous NIDDM. Diabetes 1 July 1996; 45 (7): 941–946. https://doi.org/10.2337/diab.45.7.941
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