In vivo assessment of insulin binding in different organs of growing and adult glutamate-induced obese rats.

Abstract

Injection of Na-L-glutamate into neonate Wistar-rats (2 mg/g body mass s.c.; day 1-5 of life) induces hypothalamic lesions, which are followed by hypoplastic-hypertrophic obesity despite normophagia. In contrast to other animal models of obesity, these rats develop obesity under peripheral normoinsulinemic conditions. However, beginning at an age of 2 months (growing rats), peripheral insulin concentration rises gradually and at an age of 6 months (adults rats) hyperinsulinemia becomes manifest. Surprisingly, adult rats show normoglycemia, pointing to alterations in insulin sensitivity. In continuation to previous work, insulin binding of different organs of growing and adult rats was investigated using the in vivo radioreceptor assay described by Whitcomb et al. in 1985. In contrast to in vitro methods, this assay works under real metabolic and hormonal conditions in plasma of lean and obese rats. Insulin binding of liver, pancreas, adrenals, stomach, duodenum, spleen, and heart muscles was found to be not statistically different between lean and obese rats of both age groups. Thus, liver insulin binding was 6323 +/- 458 pg/g wet organ in growing, and 7586 +/- 959 pg/g in adult lean rats. Corresponding values for obese rats were 5755 +/- 445 pg/g and 7830 +/- 526 pg/g, respectively. Organ specific down regulation of insulin binding in obese rats was not detected, suggesting unalterated insulin sensitivity. It is concluded that hyperinsulinemia of adult glutamate-induced obese rats cannot be explained by diminished insulin binding and reduced organ specific insulin clearance.