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Objective: Chronically elevated free fatty acids contribute to insulin resistance and pancreatic β-cell failure. Among numerous potential factors, the involvement of endoplasmic reticulum (ER) stress has been postulated to play a mechanistic role. Here we examined the efficacy of the chemical chaperone, sodium phenylbutyrate (PBA), a drug with known capacity to reduce ER stress in animal models and in vitro, on lipid-induced insulin resistance and β-cell dysfunction in humans.Research Design and Methods: Eight overweight or obese nondiabetic men underwent four studies each, in random order, 4 to 6 weeks apart. Two studies were preceded by 2 weeks of oral PBA (7.5 g/day), followed by a 48-h i.v. infusion of intralipid/heparin or saline, and two studies were preceded by placebo treatment, followed by similar infusions. Insulin secretion rates (ISRs) and sensitivity (S(I)) were assessed after the 48-h infusions by hyperglycemic and hyperinsulinemic-euglycemic clamps, respectively.Results: Lipid infusion reduced S(I), which was significantly ameliorated by pretreatment with PBA. Absolute ISR was not affected by any treatment; however, PBA partially ameliorated the lipid-induced reduction in the disposition index (DI = ISR × S(I)), indicating that PBA prevented lipid-induced β-cell dysfunction.Conclusions: These results suggest that PBA may provide benefits in humans by ameliorating the insulin resistance and β-cell dysfunction induced by prolonged elevation of free fatty acids. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We have previously shown that patients with restricting type anorexia nervosa (AN-R) have low plasma lipid levels, which increase with refeeding. In this study, we investigated plasma lipid levels in patients with eating disorders, distinguishing between individuals with bulimia nervosa (BN) and anorexia nervosa of the binge eating/purging type (AN-B). METHODS: We examined the fasting lipid levels in individuals with BN (n = 10) and AN-B (n = 9), and compared these findings with a group of age-matched normal weight healthy controls (C) (n = 10). RESULTS: The AN-B group had significantly higher concentrations of total plasma cholesterol, apolipoprotein (apo) B, apoA1, and low-density lipoprotein (LDL)-cholesterol than both control and BN groups (p < .05). The AN-B group also had higher plasma triglycerides and intermediate-density lipoprotein (IDL)-apo B levels (p < .05) than controls. DISCUSSION: In conclusion, the issue of hyperlipidemia in patients with eating disorders is a complex one and this study, taken together with the findings of our previous study, demonstrates the importance of carefully distinguishing between the major types of eating disorders (AN-R, BN, and AN-B) when examining plasma lipid levels. [ABSTRACT FROM AUTHOR]