Research ArticleALCOHOL ABUSE

Binge Drinking Induces Whole-Body Insulin Resistance by Impairing Hypothalamic Insulin Action

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Science Translational Medicine  30 Jan 2013:
Vol. 5, Issue 170, pp. 170ra14
DOI: 10.1126/scitranslmed.3005123

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Worse than a Hangover

For some college students, getting hammered on weekends is just part of life. But such binge drinking may be setting these young people up for diabetes. Lindtner et al. now show that rats given large doses of ethanol to simulate several wild nights of partying develop abnormal brain responses to insulin, even when the alcohol has been cleared from their system. When this brain system goes awry, the animals become generally insulin-resistant, the first step in acquiring diabetes.

The authors gave Sprague-Dawley rats a daily dose of alcohol equivalent to 7 ounces for a person. As long as 54 hours after the last drink, the rats showed signs of impaired glucose tolerance—insulin at a particular concentration was not as effective in provoking glucose uptake into body tissues. This was largely a result of decreased insulin action in the liver, which in turn prevented normal glucose uptake into the liver. Insulin also failed to induce normal lipolysis in white adipose tissue, increasing gluconeogenic substrates to the liver and further impairing liver insulin action.

Unexpectedly, insulin acted abnormally in the brain after binge drinking. Infusion of insulin directly into the hypothalamus usually suppresses liver and adipose tissue lipolysis, likely via the autonomic nervous system. But after ethanol administration, the authors found that direct treatment with insulin did not have this effect: Insulin infused into the hypothalamus did not suppress hepatic glucose production or lipolysis. Consistent with these data was the fact that, in ethanol-treated animals, biochemical markers of insulin signaling (phosphorylation of the insulin receptor and AKT phosphorylation) decreased in the brain but not in the liver.

How does the ethanol harm the hypothalamus? The authors found that rounds of binge drinking apparently trigger inflammation, as assessed by interleukin-6 and tumor necrosis factor–α levels. The tyrosine phosphatase gene PTP1B was also elevated, playing a critical role in mediating alcohol’s effect because its inhibition can restore normal glucose tolerance after binge drinking.

Whether these toxic effects of ethanol occur in partying people is not yet known, but the powerful effect of ethanol on the insulin-glucose regulatory system is certainly sobering.

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