Oral NAC supplementation to a high‐sucrose meal improves postprandial glycemic control via glutathione synthesis in rats

Abstract

Postprandial hyperglycemia may be detrimental to glucose homeostasis by promoting oxidative stress. We hypothesized that dietary cysteine may favor postprandial glucose control by maintaining glutathione (GSH) status. This work investigates the effects of moderate or high N-acetylcysteine (NAC) supplementation to a high sucrose (HS) meal on postprandial glucose homeostasis in healthy rats. In experiment 1, 3 groups of rats received a 3 g meal containing 72% of sucrose, either enriched with 5.5 g.kg−1 NAC (C1), 16 g.kg−1 NAC (C2) or not enriched (C0). Postprandial parameters were monitored for 3h. after the meal ingestion. The same measurements were performed on a second series of animals (experiment 2) that were injected 4 mmol.kg−1 BSO, a specific inhibitor of glutamate-cysteine ligase, 1 hour before the meal. In experiment 1, postprandial hyperglycemia was 15 ± 3 % and 34 ± 8 % lower (P<0.05) and postprandial hyperinsulinemia was 33 ± 12 % and 66 ± 7 % lower (P<0.05), in C1 and C2 rats, respectively, when compared to C0 rats. Insulin sensitivity, as assessed by HOMA index, was higher in C1 and C2 rats, with a NAC dose effect (P<0.05). Conversely, after BSO injection, postprandial hyperglycemia, hyperinsulinemia and HOMA index did not differ anymore between groups. In both experiment 1 and 2, postprandial GSH redox state was lower in C1 and C2 rats, as compared to C0 rats. Taken together, these data show that meal cysteine favors postprandial glycemic control through a mechanism that involves GSH synthesis and limits adverse effects of sucrose-induced oxidative stress.