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Sodium Phenylbutyrate Improves Insulin Resistance

Phenylbutyrate treatment improves β-cell dysfunction in overweight or obese men

TUESDAY, March 15 (HealthDay News) -- Sodium phenylbutyrate (PBA) may improve insulin resistance and β-cell dysfunction caused by prolonged elevation of free fatty acids (FFA) in obese or overweight individuals, according to research published in the March issue of Diabetes.

Changting Xiao, Ph.D., from the University of Toronto, and colleagues examined the effect of PBA on β-cell dysfunction and lipid-induced insulin resistance. Eight men who were either overweight or obese without diabetes underwent four studies, four to six weeks apart. In two of the studies, oral PBA (7.5 g per day) was given for two weeks followed by 48 hours of intravenous infusion of intralipid/heparin or saline. In the other two studies, infusion was preceded by two weeks of placebo treatment. After infusion, insulin secretion rates (ISRs) were assessed by hyperglycemic clamp, and insulin sensitivity by hyperinsulinemic-euglycemic clamp.

The investigators found that pretreatment with PBA significantly improved the insulin sensitivity reduction caused by lipid infusion. None of the treatments affected the absolute ISR. PBA partially improved lipid-induced reduction in the disposition index, thereby preventing lipid-induced β-cell dysfunction.

"The current study demonstrates that PBA may provide clinical benefits in humans against insulin resistance and β-cell dysfunction induced by prolonged exposure to elevated circulating FFAs. Future studies are needed to explore the mechanism of such effects and to establish the long-term benefit and safety of compounds such as PBA in prediabetic and type 2 diabetic individuals," the authors write.

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