Summary
The t1/2 of insulin removal by perfused liver from hyperinsulinaemic ob/ob mice has previously been shown to be prolonged as compared to livers from nonobese mice. Since this defect improved when insulin levels were lowered in vivo, it appeared that the abnormality might be secondary to hyperinsulinaemia. To test this hypothesis further, insulin removal by perfused liver from one year and 6 week old Sprague-Dawley rats has been compared. Older rats were both obese and hyperinsulinaemic, and their t1/2 of insulin removal (mean ± SEM) was significantly prolonged (11.0±0.56 min vs 7.6±0.29 min). In addition, the induction of severe streptozotocin-induced hypoinsulinaemia in young rats led to a shortening of the t1/2 (5.56±0.72 min). However, the t1/2 also fell comparably when weight gain of young control rats was limited to that of young hypoinsulinaemic rats by caloric restriction (5.89±0.81 min). Furthermore, t1/2 was not increased when young rats were made hyperinsulinaemic by administration of NPH insulin for 12–14 days, nor was it decreased when older rats were made moderately hypoinsulinaemic by the administration of streptozotocin. These results demonstrate that the defect in hepatic insulin removal observed in the ob/ob mouse is not unique to this genetic variant, but is also observed in normal obese rats. Although the mechanism responsible for this phenomenon remains to be defined, it does not seem to be a simple function of relatively short-term (1–2 weeks) changes in plasma insulin concentration. On the other hand, it is still possible that the prolongation of insulin removal in both the ob/ob mouse and the obese rat is secondary to more chronic elevations in plasma insulin, or, alternatively is related to the obese state itself. In either event, the defect in hepatic insulin removal may be a general feature of obesity and, as such, contribute to the maintenance of hyperinsulinaemia in a variety of states characterized by obesity.
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Weiland, D., Mondon, C.E. & Reaven, G.M. Prolongation of insulin removal by perfused liver from spontaneously obese rats. Diabetologia 16, 173–177 (1979). https://doi.org/10.1007/BF01219794
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DOI: https://doi.org/10.1007/BF01219794