Total pancreatic insulin, dynamic insulin response to glucose (325 mg/dl), or tolbutamide (40 mg/dl) using the isolated perfused pancreas preparation and body composition were determined for 2- and 4-wk-old homozygous lean Fa/Fa, heterozygous lean Fa/fa, unknown lean Fa/??, and homozygous obese fa/fa female Zucker rats. At 2-wk, obese rats (body fat >16%) released significantly more insulin than homozygous lean rats during first (min 10-16) and second phases (min 17-70) (61 vs. 30 ng and 637 vs. 255 ng, respectively). Plasma insulinemia was 177 μU/ml in obese, compared with 51 μU/ml in homozygous lean rats. The dynamic response of unknown lean followed the pattern of either the homozygous lean or the obese rats. There was no significant difference in total pancreatic insulin among any of the groups at 2 wk of age (Fa/Fa, 1.72; Fa/??, 2.01; and Fa/Fa, 1.80 μg). At 4 wk, the dynamic response by obese (2.98 μg) was similar to that of heterozygous (3.31 μg), both being significantly greater than the homozygous lean (1.14 μg) or unknown lean rats (1.77 μg). Total pancreatic insulin in 4-wk obese (19.8 μg) was greater than homozygous lean rats (14.5 μg). Tolbutamide-stimulated insulin release was significantly greater in 4-wk obese than homozygous lean rats. Exposure to tolbutamide reduced by 60% the second-phase insulin release in both obese and homozygous lean rats during a subsequent 40-min glucose (325 mg/dl) perfusion. The presence of a greater dynamic release despite similar total pancreatic insulin (obese vs. homozygous lean) at 2 wk of age suggests a mechanism for the hyperinsulinemic response to glucose by the 2nd wk of life. More importantly, though, the data demonstrate a heterozygote effect at both 2 and 4 wk of age with respect to plasma insulin and at 4 wk of age with respect to insulin released during pancreatic perfusion in vitro with glucose. This points out a need to differentiate between lean and heterozygote rats when studying phenotypically lean Fa/?? rats.
|Original language||English (US)|
|Journal||American Journal of Physiology - Endocrinology and Metabolism|
|State||Published - 1985|
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