Dataset Information

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

ABSTRACT:

Context

Hypoglycemia, one of the major factors limiting optimal glycemic control in insulin-treated patients with diabetes, elicits a brain response to restore normoglycemia by activating counterregulation. Animal data indicate that local release of norepinephrine (NE) in the hypothalamus is important for triggering hypoglycemia-induced counterregulatory (CR) hormonal responses.

Objective

To examine the potential role of brain noradrenergic (NA) activation in humans during hypoglycemia.

Design

A hyperinsulinemic-hypoglycemic clamp was performed in conjunction with positron emission tomographic 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 NE 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 NA response in humans. Raphe nuclei, a region involved in regulating autonomic output, motor activity, and hunger, had increased NA activity, whereas the hypothalamus showed a NET-binding pattern that was associated with the individual's CR response magnitude. These findings suggest that NA output most likely is important for modulating brain responses to hypoglycemia in humans.

SUBMITTER: Belfort-DeAguiar R

PROVIDER: S-EPMC6456998 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Belfort-DeAguiar Renata R Gallezot Jean-Dominique JD Hwang Janice J JJ Elshafie Ahmed A Yeckel Catherine W CW Chan Owen O Carson Richard E RE Ding Yu-Shin YS Sherwin Robert S RS

The Journal of clinical endocrinology and metabolism 20180601 6

<h4>Context</h4>Hypoglycemia, one of the major factors limiting optimal glycemic control in insulin-treated patients with diabetes, elicits a brain response to restore normoglycemia by activating counterregulation. Animal data indicate that local release of norepinephrine (NE) in the hypothalamus is important for triggering hypoglycemia-induced counterregulatory (CR) hormonal responses.<h4>Objective</h4>To examine the potential role of brain noradrenergic (NA) activation in humans during hypogly ...[more]

PMID: 29590401

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Dataset Information

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

Context

Objective

Design

Participants

Design

Results

Conclusions

Publications

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

Similar Datasets

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