Cellular basis of direct insulin action in the central nervous system.

The in vivo radioautographic method has been applied to elucidate the mechanism of direct peptide hormone "feedback" action in the CNS. Using this method we have identified the circumventricular organs of the brain as general endocrine target tissues for a variety of blood-borne polypeptide hormones, including insulin. In the arcuate-median eminence region of the hypothalamus blood-borne insulin directly interacts with receptive nerve terminals, suggesting that insulin acts to influence the electrical activity of select hypothalamic nerve circuits at the level of synaptic transmission. Recent results obtained from preliminary surgical and chemical lesion studies of brain indicate that insulin-receptive nerve terminals in the arcuate-median eminence region arise from neurons intrinsic to the medial basal hypothalamus. This has lead us to propose the concept of the hypothalamic tuberoinfundibular insulin-receptive neuron and its axon collaterals as a pathway for the centripetal flow of insulin "signals" in the form of electrical impulses. We envisage that the neuroanatomic pathway, provided by the hypothalamic tuberoinfundibular neuron, functions to link changes in the body metabolic activity, as reflected in changing levels of circulating insulin, to the neuronal process of elaborating specific central metabolic-regulatory programs. This pathway could be of key importance in understanding and combating metabolic disease.