Noradrenergic Activity in the Human Brain: A Mechanism Supporting the Defense Against Hypoglycemia.

Noradrenergic Activity in the Human Brain: A Mechanism Supporting the Defense Against Hypoglycemia.

J Clin Endocrinol Metab. 2018 Mar 23;:

Authors: Belfort-DeAguiar RD, Gallezot JD, Hwang JJ, Elshafie A, Yeckel CW, Chan O, Carson RE, Ding YS, Sherwin RS

Abstract
Context: Hypoglycemia, one of the major factors limiting optimal glycemic control in insulin-treated diabetic patients, elicits a brain response to restore normoglycemia by activating counterregulation. Animal data indicate that local release of norepinephrine in the hypothalamus is important for triggering hypoglycemia-induced counterregulatory (CR) hormonal responses.
Objective: To examine the potential role of brain noradrenergic activation in humans during hypoglycemia.
Design: A hyperinsulinemic-hypoglycemic clamp was performed in conjunction with PET imaging.
Participants: Nine lean healthy volunteers were studied during the hyperinsulinemic-hypoglycemic clamp.
Design: Participants received intravenous injections of (S,S)-[11C]O-methylreboxetine, [11C]MRB, a highly selective norepinephrine transporter (NET) ligand, at baseline and during hypoglycemia.
Results: Hypoglycemia increased plasma epinephrine, glucagon, cortisol and growth hormone, and decreased [11C]MRB binding potential (BPND) by 24 ± 12% in the raphe nucleus (P<0.01). In contrast, changes in [11C]MRB (BPND) in the hypothalamus positively correlated with increments in epinephrine and glucagon levels and negatively correlated with glucose infusion rate (all P<0.05). Furthermore, in rat hypothalamus studies, hypoglycemia induced NET translocation from the cytosol to the plasma membrane.
Conclusions: Insulin-induced hypoglycemia initiated a complex brain noradrenergic response in humans. Raphe nuclei, a region involved in regulating autonomic output, motor activity and hunger, was observed to have increased noradrenergic activity, while the hypothalamus showed a NET-binding pattern that was associated with the individual's CR response magnitude. These findings suggest that noradrenergic output most likely is important for modulating brain responses to hypoglycemia in humans.

PMID: 29590401 [PubMed - as supplied by publisher]

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