IN-VIVO ASSESSMENT OF INSULIN BINDING IN DIFFERENT ORGANS OF GROWING AND ADULT GLUTAMATE-INDUCED OBESE RATS

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 fol lowed by hypoplastic-hypertrophic obesity despite normophagia. In cont rast to other animal models of obesity, these rats develop obesity und er peripheral normoinsulinemic conditions. However, beginning at an ag e of 2 months (growing rats), peripheral insulin concentration rises g radually and at an age of 6 months (adult rats) hyperinsulinemia becom es 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 inve stigated using the in vivo radioreceptor assay described by Whitcomb e t al. in 1985. In contrast to in vitro methods, this assay works under real metabolic and hormonal conditions in plasma of lean and obese ra ts. Insulin binding of liver, pancreas, adrenals, stomach, duodenum, s pleen, and heart muscle was found to be not statistically different be tween lean and obese rats of both age groups. Thus, liver insulin bind ing 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 regu lation of insulin binding in obese rats was not detected, suggesting u nalterated insulin sensitivity. It is concluded that hyperinsulinemia of adult glutamate-induced obese rats cannot be explained by diminishe d insulin binding and reduced organ specific insulin clearance.