Failure of chronic experimental hyperinsulinism to alter insulin binding to hypothalamic receptors in the rat

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Abstract
[125I]insulin binding to medial hypothalamic receptors is attenuated following 14 days of food restriction. Such rats are characterized by considerably reduced circulating insulin levels with unchanged hypothalamic insulin concentration. In contrast to the effects of starvation, [125I]insulin binding to hypothalamic receptors from rats made hyperinsulinemic by daily injections of protamine zinc insulin (4-6 U/rat per day for 14 days) is unaffected by this manipulation, even though hypothalamic insulin concentration in insulin-injected animals was significantly higher than in saline-injected controls. Insulin binding to partially purified membranes from the medial hypothalamic region was significantly greater than that from the lateral area. Insulin treatment was associated with slight reductions in maximal insulin-binding capacity of medial hypothalamic receptors, a tendency which appeared to be compensated by reciprocal changes in receptor affinity for this hormone. Hypothalamic insulin receptors are not regulated by peripheral or even central insulin levels per se; it appears, rather, that some other, as yet unidentified, correlate(s) of significantly altered food intake and/or body weight can modify hypothalamic insulin receptor function. Perhaps such modifications could, in turn, participate in the activation of regulatory mechanisms involved in correcting energy imbalance.

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