Glucose-6-Phosphatase Activity Is Not Suppressed but the mRNA Level Is Increased by a Sucrose-Enriched Meal in Rats

Abstract

The expression of glucose-6-phosphatase (G6Pase) mRNA is repressed by insulin and stimulated by cAMP and dexamethasone, with the insulin effect dominant. Both lipids and glucose increase the expression of G6Pase mRNA under conditions in which insulin is either absent or at basal levels. The aim of the present study was to investigate dietary nutrient regulation of G6Pase mRNA and protein under postprandial conditions. Male rats (n = 6-8/group) were deprived of food for 48 h and then either remained food deprived (FD) or were refed diets containing 68% cornstarch and 12% corn oil (ST; % energy), 68% sucrose and 12% corn oil (SU) or 35% cornstarch and 45% corn oil (HF) for 3 h. Rats were anesthetized, blood was drawn from the portal vein, and the liver was removed and immediately processed for subsequent analyses. Energy intake over the 3-h refeeding period did not differ among groups (209 +/- 25 kJ). Portal vein glucose and insulin were 5.0 +/- 0.2 mmol/L and 90 +/- 18 pmol/L, respectively, in FD rats and were not significantly different among the refed groups (14.5 +/- 1.2 mmol/L and 1302 +/- 154 pmol/L, respectively). Compared with the FD rats, G6Pase mRNA was approximately 50% lower in ST and HF groups, whereas it was approximately 1.6 fold higher in SU-refed rats (P < 0.05). G6Pase activity in whole liver homogenates was lower in ST and HF rats than in FD and SU rats. Insulin receptor substrate (IRS) phosphorylation, IRS-association with phosphatidylinositol 3 (PI3)-kinase and activation of protein kinase B (PKB) were not significantly different among the refed groups. However, glycogen synthase kinase-3alpha phosphorylation was lower and cAMP response element binding protein (CREB) phosphorylation was higher in SU rats than in ST and HF refed groups. Thus, the postprandial environment after ingestion of sucrose appears to overcome the dominant effects of insulin on G6Pase mRNA, perhaps via cellular changes that reduce phosphorylation of, and therefore activate, glycogen synthase kinase-3alpha.