EFFECTS OF FRUCTOSE-RICH DIET AND CHRONIC STRESS ON INSULIN SIGNALING AND REGULATION OF GLYCOGEN SYNTHASE KINASE-3 BETA AND SODIUM-POTASSIUM PUMP IN THE HEART OF MALE RATS
Both diet rich in fructose and chronic stress exposure induce metabolic and cardiovascular disturbances. The aim of this study was to examine effects of fructose-rich diet and chronic stress, separately and in combination, on insulin signaling and molecules regulating glycogen synthesis and ion transport in the heart, and to reveal whether those effects coincide with changes in glucocorticoid receptor (GR) activation. Male Wistar rats were subjected to 10% fructose in drinking water and/or to chronic unpredictable stress during 9 weeks. Protein expression and/or phosphorylation of insulin receptor (IR), protein tyrosine phosphatase 1B, insulin receptor substrate 1 (IRS1), protein kinase B (Akt), extracellular signal-regulated kinase 1/2 (ERK1/2), glycogen synthase kinase-3β (GSK-3β) and Na+/K+-ATPase α-subunits in cardiac tissue were analyzed by Western blot. GR distribution between cytosolic and nuclear fraction was also analyzed. Fructose-rich diet decreased level of pERK1/2 (Thr202/Tyr204) and pGSK-3β (Ser9) independently of stress, while chronic stress increased IRS1 content and prevented fructose diet-induced decrease of pAkt (Ser473) level. Fructose-rich diet in combination with chronic stress reduced protein content of cardiac IR and attenuated IRS1 upregulation. Separate treatments increased protein content of Na+/K+-ATPase α1- and α2-subunit, while after combined treatment α2 content was at the control level and α1 content was lower than control. Effect of combined treatment on cardiac IR and α2-subunit expression could be mediated by increased GR nuclear accumulation. Our study provides new insights on effects of chronic stress and combination of fructose diet and chronic stress on studied molecules in the heart.