Ultimate glucose monitor - brain

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Hi All,

It seemed worth considering the full-text-free-to-all-available paper:

Kubota N, Terauchi Y, Tobe K, Yano W, Suzuki R, Ueki K, Takamoto I, Satoh H,

Maki T,

Kubota T, Moroi M, Okada-Iwabu M, Ezaki O, Nagai R, Ueta Y, Kadowaki T, Noda T.

Insulin receptor substrate 2 plays a crucial role in beta cells and the

hypothalamus.

J Clin Invest. 2004 Oct;114(7):917-27.

PMID: 15467830

http://www.jci.org/cgi/content/full/114/7/917

The study found, regarding the hypothalamus, that in insulin receptor knockout

mice:

" ... Despite their normal insulin sensitivity at 8 weeks with caloric

restriction,

the betaHT-IRS2 mice exhibited glucose intolerance and impaired glucose-induced

insulin secretion. ... "

The below pdf-available paper, for which an introduction is provided, seems to

say

the glucose levels in the hypothalamus are instrumental in regulating the serum

level of glucose.

Science. 2005 Aug 5;309(5736): ?

The Ultimate Glucose Monitor

The brain, and in particular, the hypothalamus, controls liver glucose

production,

but the cellular and molecular mechanisms by which the brain senses glucose

levels

have been unclear. Lam et al. (p. 943) now show that, in rats, this process

requires

the conversion of glucose in the hypothalamus to lactate, which in turn

stimulates

pyruvate metabolism and adenosine triphosphate (ATP) production. Alterations in

ATP

levels control neuronal excitability through effects on ATP-sensitive potassium

channels, which have been implicated in glucose output by the liver.

Lam TK, Gutierrez-Juarez R, Pocai A, Rossetti L.

Regulation of blood glucose by hypothalamic pyruvate metabolism.

Science. 2005 Aug 5;309(5736):943-7.

PMID: 16081739

The brain keenly depends on glucose for energy, and mammalians have redundant

systems to control glucose production. An increase in circulating glucose

inhibits

glucose production in the liver, but this negative feedback is impaired in type

2

diabetes. Here we report that a primary increase in hypothalamic glucose levels

lowers blood glucose through inhibition of glucose production in rats. The

effect of

glucose requires its conversion to lactate followed by stimulation of pyruvate

metabolism, which leads to activation of adenosine triphosphate (ATP)-sensitive

potassium channels. Thus, interventions designed to enhance the hypothalamic

sensing

of glucose may improve glucose homeostasis in diabetes.

Al Pater, PhD; email: old542000@...

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