Thymoquinone normalizes insulin secretion from pancreatic β-cells under glucose overload. - GreenMedInfo Summary
Thymoquinone, a bioactive component of Nigella sativa, normalizes insulin secretion from pancreaticβ-cells under glucose overload via regulation of malonyl-CoA.
Am J Physiol Endocrinol Metab. 2016 Jan 19:ajpendo.00250.2015. Epub 2016 Jan 19. PMID: 26786775
Joshua P Gray
Thymoquinone (2-Isopropyl-5-methylbenzo-1,4-quinone) is a major bioactive component of Nigella sativa, a plant used in traditional medicine to treat variety of symptoms, including elevated blood glucose levels in type 2 diabetic patients. Normalization of elevated blood glucose depends on both glucose disposal by peripheral tissues, and glucose-stimulated insulin secretion (GSIS) from pancreaticβ-cells. We employed clonal β-cells and rodent islets to investigate the effects of Thymoquinone (TQ) and Nigella sativa extracts (NSEs) on GSIS and cataplerotic metabolic pathways implicated in the GSIS regulation. TQ and NSE regulated NAD(P)H/NAD(P)(+) ratios via a redox cycling mechanism. TQ content was positively correlated with the degree of redox cycling activity of NSE extracts, suggesting that TQ is a major component engaged in mediating NSE-dependent redox cycling. Both acute and chronic exposure to TQ and NSE enhanced GSIS and were associated with the ability of TQ and NSE to increase the ATP/ADP ratio. Furthermore, TQ ameliorated the impairment of GSIS following chronic exposure of β-cells to glucose overload (GO). This protective action was associated with the TQ-dependent normalization of chronic accumulation of malonyl CoA, and elevation of acetyl CoA carboxylase (ACC),fatty acid synthase (FAS) and fatty acid binding proteins (FABPs) following chronic glucose overload. Together these data suggest that TQ modulates the β-cell redox circuitry, and enhances the sensitivity of β-cell metabolic pathways to glucose and GSIS under both normal conditions and hyperglycemia. This action is associated with the ability of TQ to regulate carbohydrate-to-lipid flux via downregulation of acetyl-CoA carboxylase (ACC) and malonyl-CoA.