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

Abstract

We have tested the hypothesis that insulin affects the metabolism of the hypothalamus 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 [ I25 I]-iodoinsulin by ventral medial, lateral and far lateral segments of hypothalamus, median eminence, basal ganglia, and cerebral cortex was compared to that of two 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 to 20 times greater than the brain tissues.The uptake, oxidation and formation of lipid from [ 14 C]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. Alternatively, we cannot exclude the possibility that insulin might directly alter the permeability of the blood-brain barrier for nutrients in the hypothalamic region. {Endocrinology 101: 605, 1977) S EVERAL investigations have provided indirect evidence that control systems integrated within the hypothalamus are influenced by insulin. Mayer (1) was the first to postulate that the glucoreceptors of the hypothalamus concerned with feeding behavior were insulin-sensitive structures. This hypothesis was tested by Debons et al.(2), who demonstrated that diabetic mice were resistant to hypothalamic damage by gold thioglucose unless they were treated with insulin. Insulin injected directly into the hypothalamus also restored sensitivity to gold-thioglucose (3). Szabo and Szabo (4) have shown that intracarotid injection of insulin results in a change of peripheral blood glucose which they ascribe to an effect of insulin within the central nervous system upon glucoregulatory systems. A number of investigators have demonstrated

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“…Thus, the available data suggest that insulin affects glucose storage in brain in a manner that is qualitatively similar to that in other tissues. With respect to other aspects of brain glucose metabolism, studies have shown effects of insulin on brain glucose utilization (26)(27)(28)(29)(30)(31)(32) or no effect (33)(34)(35)(36)(37)(38)(39)(40).…”

Insulin dysfunction and Tau pathology

“…In the past, the brain was described as “an insulin insensitive organ” (Goodner and Berrie, 1977). However, it is currently well known that insulin and its receptors are widely present in the CNS (Baskin et al, 1988; Lerorrtt et al, 1988; for review, see Schulingkamp et al, 2000).…”

Insulin and insulin receptors in rodent brain

“…What is the role of insulin in the CNS? Insulin effects on glucose metabolism in the CNS are controversial; some authors found slight but definite effects [19], while others did not find any at all [20]. The unchanging brain insulin levels during profound alterations of plasma glucose and insulin probably points away from a significant role for insulin in brain glucose metabolism.…”