Role of apoptosis in failure of beta-cell mass compensation for insulin resistance and beta-cell defects in the male Zucker diabetic fatty rat.

摘要: To define the mechanisms involved in evolution of diabetes Zucker diabetic fatty (ZDF) rat, beta-cell mass and replication rates were determined by immunochemistry, point-counting morphometry, 6-h 5-bromo-2'-deoxyuridine (BrdU) incorporation. The 5- to 7-week-old prediabetic ZDF rats (4.3 +/- 0.06 mg) was similar age-matched insulin-resistant (ZF) (3.7 0.05 greater than that lean control (ZLC) (1.9 0.3, P < 0.05). At 12 weeks (after onset), (8.1 1.7 significantly lower ZF (15.7 1.8 mg). ZLC 0.8 mg, proliferation rate (mean both time points) (0.88 0.1%) compared with (0.53 0.07%, 0.62 respectively, 0.05), yet have a despite higher proliferative rate. Morphological evidence neogenesis apoptosis is evident rats. In addition, even at 5-7 modest defect insulin secretion per unit found pancreas perfusion. These studies provide expansion response resistance secretory defects inadequate. This failure rat does not appear be from reduction or neogenesis, suggesting an increased cell death apoptosis.