Hypothalamic nitric oxide in hypoglycemia detection and counterregulation: a two-edged sword
Antioxidants & Redox Signaling. 2011-02-01; 14(3): 505-517
DOI: 10.1089/ars.2010.3331
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1. Antioxid Redox Signal. 2011 Feb 1;14(3):505-17. doi: 10.1089/ars.2010.3331.
Epub 2010 Aug 17.
Hypothalamic nitric oxide in hypoglycemia detection and counterregulation: a
two-edged sword.
Fioramonti X(1), Song Z, Vazirani RP, Beuve A, Routh VH.
Author information:
(1)Department of Pharmacology and Physiology, New Jersey Medical School, Newark,
New Jersey 07101-1709, USA.
Hypoglycemia is the main complication for patients with type 1 diabetes mellitus
receiving intensive insulin therapy. In addition to the obvious deleterious
effects of acute hypoglycemia on brain function, recurrent episodes of
hypoglycemia (RH) have an even more insidious effect. RH impairs the ability of
the brain to detect and initiate an appropriate counterregulatory response (CRR)
to restore euglycemia in response to subsequent hypoglycemia. Knowledge of
mechanisms involved in hypoglycemia detection and counterregulation has
significantly improved over the past 20 years. Glucose sensitive neurons (GSNs)
in the ventromedial hypothalamus (VMH) may play a key role in the CRR. VMH
nitric oxide (NO) production has recently been shown to be critical for both the
CRR and glucose sensing by glucose-inhibited neurons. Interestingly, downstream
effects of NO may also contribute to the impaired CRR after RH. In this review,
we will discuss current literature regarding the molecular mechanisms by which
VMH GSNs sense glucose. Putative roles of GSNs in the detection and initiation
of the CRR will then be described. Finally, hypothetical mechanisms by which VMH
NO production may both facilitate and subsequently impair the CRR will be
discussed.
DOI: 10.1089/ars.2010.3331
PMCID: PMC3025177
PMID: 20518706 [Indexed for MEDLINE]