It is well established that local glucoprivation at the VMH stimulates glucose inhibitory neurons and acute noradrenergic activity (NA) therein necessary for the sympathoadrenal counter regulatory response to such glucoprivation. However, paradoxically a wide variety of insulin resistant, glucose intolerant, hyperglycemic animal models exhibit chronic elevation of NA at the VMH. Further, chronic VMH infusion of NE to normal animals leads to insulin resistance and glucose intolerance similar to that observed following sustained exposure to a high fat diet. Since VMH glucose excitatory neurons are activated by physiological postprandial increase in local glucose level to increase peripheral insulin action, these VMH NA findings suggest a novel function of elevated VMH NA to block normal postprandial glucose sensing of VMH glucose excitatory (GE) neurons that potentiate postprandial insulin sensitivity. To test this postulate multi-barreled pipettes with carbon fiber recording electrodes were lowered into the VMH of anesthetized rats (N=10) (age 12 weeks, maintained on standard low fat rodent chow diet) and multi-unit responses (MURs) from the central recording electrode (∼.5 Mω) before and during glucose electro-osmotic injection into the VMH (to preferentially activate GE neurons) were obtained. Changes in MURs to such glucose administration (that were at least 15% above baseline, P<0.05) were compared when such glucose was co-administered with micro-iontophoretically injected NE and such NE treatment significantly and consistently reduced such glucose-induced MURs by 46% (P<0.05). Among those glucose-induced MURs greater than 100% above baseline, this NE inhibition was even greater (50%, P<0.05). These findings are the first to identify a novel role for increased VMH NA in the blockade of normal postprandial VMH glucose sensing that is involved in increasing subsequent post-meal peripheral insulin action.
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