Abstract

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.

摘要

通过调节肝糖代谢，过量摄入果糖饮料和日常压力会导致代谢异常。该研究的目的是研究高果糖饮食与慢性应激的相互作用是否会改变胰岛素和糖皮质激素的信号传导，从而影响肝糖稳态。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）磷酸化升高，葡萄糖激酶mRNA和磷酸-总糖原合酶激酶3比例增加以及糖异生基因的表达降低。果糖饮食也导致糖皮质激素前体受体代谢受刺激，但由于糖皮质激素清除率增加，下游信号保持不变。应激不影响肝胰岛素和糖皮质激素信号传导，也不影响葡萄糖代谢，而仅针对葡萄糖激酶表达观察到这些因素的相互作用。结果表明，在果糖诱导的高胰岛素血症的情况下，糖异生和糖原合酶激活的抑制有助于维持葡萄糖稳态。糖皮质激素失活增加可能是预防高血糖症的适应性机制。