Department of Biochemistry, Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia.
Department of Physiology, University of Lausanne, UNIL-CHUV, Lausanne, Switzerland.
Int J Food Sci Nutr. 2020 Nov;71(7):815-825. doi: 10.1080/09637486.2020.1728236. Epub 2020 Feb 18.
Overconsumption of fructose-enriched beverages and everyday stress are involved in the pathogenesis of metabolic disorders through modulation of hepatic glucose metabolism. The aim of the study was to investigate whether interaction of high-fructose diet and chronic stress alter insulin and glucocorticoid signalling thus affecting hepatic glucose homeostasis. High-fructose diet led to hyperinsulinemia, increased glucose transporter 2 level, elevated protein kinase B (Akt) phosphorylation, increased glucokinase mRNA and phospho-to-total glycogen synthase kinase 3 ratio and decreased expression of gluconeogenic genes. Fructose diet also led to stimulated glucocorticoid prereceptor metabolism, but downstream signalling remained unchanged due to increased glucocorticoid clearance. Stress did not affect hepatic insulin and glucocorticoid signalling nor glucose metabolism, while the interaction of the factors was observed only for glucokinase expression. The results suggest that, under conditions of fructose-induced hyperinsulinemia, suppression of gluconeogenesis and glycogen synthase activation contribute to the maintenance of glucose homeostasis. The increased glucocorticoid inactivation may represent an adaptive mechanism to prevent hyperglycaemia.
过量摄入富含果糖的饮料和日常压力会通过调节肝脏葡萄糖代谢而导致代谢紊乱的发病机制。本研究的目的是研究高果糖饮食和慢性应激的相互作用是否会改变胰岛素和糖皮质激素信号转导，从而影响肝脏葡萄糖稳态。高果糖饮食导致高胰岛素血症、葡萄糖转运蛋白 2 水平升高、蛋白激酶 B（Akt）磷酸化增加、葡萄糖激酶 mRNA 增加和磷酸化糖原合酶激酶 3 与总比值增加以及糖异生基因表达降低。果糖饮食还导致糖皮质激素前体代谢增加，但由于糖皮质激素清除增加，下游信号转导保持不变。应激不影响肝脏胰岛素和糖皮质激素信号转导或葡萄糖代谢，而这些因素的相互作用仅观察到葡萄糖激酶的表达。结果表明，在果糖引起的高胰岛素血症的情况下，抑制糖异生和糖原合酶激活有助于维持葡萄糖稳态。增加的糖皮质激素失活可能代表一种防止高血糖的适应性机制。
