The Failure of Rat Hypothalamic Tissues to Take up Labeled Insulin in Vivo or to Respond to Insulin in Vitro

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Abstract
The hypothesis that insulin affects the metabolism of the hypothalamus was tested by examining the uptake of labeled insulin by rat brain structures in vivo and the responsiveness of the metabolism of rat brain to the addition of insulin in vitro. The uptake of immunoprecipitable [125I]-iodoinsulin by ventral medial, lateral and far lateral segments of hypothalamus, median eminence, basal ganglia and cerebral cortex was compared to that of 2 insulin-sensitive tissues, pituitary and heart muscle. Of the brain tissues only median eminence, in the region of the primary plexus, displayed significant uptake over background. Heart muscle displayed an uptake of insulin 3 times greater than median eminence and 10-20 times greater than the brain tissues. The uptake, oxidation and formation of lipid from [14C]glucose in slices of anterior and posterior hypothalamus and cortical grey matter failed to respond to insulin in vitro while diaphragm muscle from the same rats responded to insulin under identical conditions. The data fail to support the hypothesis and suggest that insulin does not directly interact with the neurons in hypothalamic nuclei but rather acts indirectly to affect hypothalamic function. The data suggest that insulin may interact with receptors in the median eminence, or other circumventricular organs, transmitting information via neuronal pathways to deeper brain centers. Insulin alternatively might directly alter the permeability of the blood-brain barrier for nutrients in the hypothalamic region.