Binding of Insulin by Monkey and Pig Hypothalamus

Abstract

Membrane preparations from monkey and pig hypothalami bound [125I]insulin specifically. The binding appeared to be greater by preparations from anterior than posterior portions of the pig hypothalamus. Binding was time dependent, and its dissociation was first order with a half-time at 22 degrees C of 14 min. Desalanine insulin was as effective as native insulin in inhibiting the binding of [125I]insulin, while proinsulin was less effective and desoctapeptide insulin still less effective in accord with their biologic activities. Binding by membranes from cortex and thalamus appeared to be less than from hypothalamus. [125I]insulin was infused into an arterial split monkey brain preparation to determine if insulin that was blood borne bound specifically to the primate hypothalamus. Half the brain was perfused with [125I]insulin alone and the other half with [125I]insulin plus an excess of unlabeled insulin. Radioautography showed specific binding of insulin localized to the median eminence, infundibular nucleus, and microvessels. Thus, the monkey and pig hypothalami bind insulin with characteristics similar to those reported for known target tissues for insulin. Furthermore, insulin from the blood stream binds to specific anatomical structures in the hypothalamus of the monkey.

Insulin in the Brain: Its Pathophysiological Implications for States Related with Central Insulin Resistance, Type 2 Diabetes and Alzheimer’s Disease

“…Since then, a wide but uneven distribution of IR in the CNS has been reported. Accordingly, it was shown that membrane preparations from the hypothalami specifically bound greater [ 125 I]insulin than membranes from the cortex and thalamus, and that this binding was higher for preparations from the anterior rather than the posterior portions of the hypothalamus ( 54 ). Likewise, the binding of [ 125 I]insulin was high not only in all olfactory areas and in closely related limbic regions, but also in the neocortex and accessory motor areas of the basal ganglia, hippocampus, cerebellum, and choroid plexus, which suggested a neuromodulatory function for insulin in the brain ( 55 ).…”

Awake, long-term intranasal insulin treatment does not affect object memory, odor discrimination, or reversal learning in mice

“…Intranasal delivery (IND) of insulin provides a safe, feasible, and effective route of administration, largely bypassing the blood-brain barrier (BBB) and maximizing distribution to the CNS [5]. Insulin receptor (IR) kinase is located throughout the brain and with high density in the olfactory bulb (OB), piriform cortex, hypothalamus, and hippocampus [6]; brain areas that also happen to have a high binding affinity for insulin [7,8,9]. Peripheral insulin is thought to bypass the BBB, via a saturable, active transport system [10, 11] allowing binding of insulin to IR kinase to elicit dimerization of the receptor followed by autophosphorylation.…”

Hypothalamic Insulin Resistance in Obesity: Effects on Glucose Homeostasis

“…Accordingly, membrane preparations from the monkey and pig hypothalami showed higher 125 I-insulin-binding activity in the anterior rather than the posterior parts of the hypothalamus [59]. High 125 I-insulin-binding activity was also detected all olfactory areas, limbic regions, neocortex and accessory motor areas of the basal ganglia, hippocampus, cerebellum, and choroid plexus, which suggested a regulatory role of insulin in the brain [60].…”