The evolution of diabetes in the male leptin receptor؊deficient (fa/fa) Zucker diabetic fatty (ZDF) rat is associated with disruption of normal islet architecture, ␤-cell degranulation, and increased ␤-cell death. It is unknown whether these changes precede or develop as a result of the increasing plasma glucose, or whether the increased ␤-cell death can be prevented. Early intervention with thiazolidinediones prevents disruption of the islet architecture. To determine the specific effects of rosiglitazone (RSG) on ␤-cell mass dynamics, male fa/fa (obese) and ؉/fa or ؉/؉ (lean) rats age 6 weeks were fed either chow (control group [CN]) or chow mixed with rosiglitazone (RSG group) at a dosage of 10 mol ⅐ kg ؊1 body wt ⅐ day ؊1 . Rats were killed after 0, 2, 4, 6, or 10 weeks of treatment (at age 6, 8, 10, 12, or 16 weeks). Plasma glucose increased from 8.9 ؎ 0.4 mmol/l at 0 weeks to 34.2 ؎ 1.8 mmol/l (P ‫؍‬ 0.0001) at 6 weeks of treatment in obese CN rats and fell from 8.0 ؎ 0.3 to 6.3 ؎ 0.4 mmol/l in obese RSG rats (P ‫؍‬ 0.02). ␤-cell mass fell by 51% from 2 to 6 weeks of treatment (ages 8 -12 weeks) in obese CN rats (6.9 ؎ 0.9 to 3.4 ؎ 0.5 mg; P < 0.05), whereas ␤-cell mass was unchanged in obese RSG rats. At 10 weeks of treatment (age 16 weeks), ␤-cell mass in obese CN rats was only 56% of that of obese RSG rats (4.4 ؎ 0.4 vs. 7.8 ؎ 0.3 mg, respectively; P ‫؍‬ 0.0001). The ␤-cell replication rate fell from a baseline value of 0.95 ؎ 0.12% in lean rats and 0.94 ؎ 0.07% in obese rats (at 0 weeks) to ϳ0.3-0.5% in all groups by 6 weeks of treatment (age 12 weeks). After 10 weeks of treatment, ␤-cell replication was higher in obese RSG rats than in CN rats (0.59 ؎ 0.14 vs. 0.28 ؎ 0.05%, respectively; P < 0.02). Application of our mass balance model of ␤-cell turnover indicated that net ␤-cell death was fivefold higher in obese CN rats as compared with RSG rats after 6 weeks of treatment (age 12 weeks). The increase in ␤-cell death in obese CN rats during the 6-week observation period was well correlated with the increase in plasma glucose (r 2 ‫؍‬ 0.90, P < 0.0001). These results suggest that the development of hyperglycemia in ZDF rats is concomitant with increasing net ␤-cell death. ␤-cell proliferation compensates for the increased ␤-cell loss at a time when plasma glucose is moderately elevated, but compensation ultimately fails and the plasma glucose levels increase beyond ϳ20 mmol/l. Treatment with rosiglitazone, previously shown to reduce insulin resistance, prevents the loss of ␤-cell mass in obese ZDF rats by maintaining ␤-cell proliferation and preventing increased net ␤-cell death.

No abstract

Total body water, mean daily water flux, and plasma ionic and osmotic concentrations were determined in sham-operated and cecally ligated male and female Pekin ducks, Anas platyrhynchos, drinking fresh water and after acclimation to 0.3 M NaCl. Body mass, hematocrit, plasma sodium concentration, and osmolality were unaffected by saline acclimation or cecal ligation. Total body water of ducks acclimated to fresh water was about 63% of body mass and increased to 73% of body mass in all groups acclimated to 0.3 M NaCl except ligated females. Mean daily water flux of male and female ducks acclimated to fresh water was the same and was not affected by cecal ligation. Drinking 0.3 M NaCl increased mean daily water flux by 70% in both sham-operated male (P < 0.05) and female ducks (P < 0.01), and 135% (P < 0.001) in cecally ligated males, but did not affect cecally ligated females. Thus, following saline acclimation, mean daily water flux was greater (P < 0.05) in cecally ligated males than in females.

No abstract