Sucrose diets increase glucose-6-phosphatase and glucose release and decrease glucokinase in hepatocytes

A high-sucrose diet (SU) decreases insulin action in the liver (Pagliassott i MJ, Shahrokhi KA, and Moscarello M. Am J Physiol Regulatory Integrative C omp Physiol 266: R1637-R1644, 1994). The present study was conducted to cha racterize the effect of SU on glucagon action in isolated periportal (PP) a nd perivenous (PV) hepatocytes by measuring glucagon-stimulated glycogenoly sis and glucose release. Male rats were fed a SU (68% sucrose) or starch di et (ST, 68% starch) for 1 wk, and hepatocytes were isolated from PP or PV r egions (n = 4/diet/cell population). Hepatocytes were incubated for 1 h in the presence of varying concentrations of glucagon (0-100 nM). In PP and PV cells, glucagon stimulation of glucose release and glycogenolysis (sum of glucose release and lactate accumulation) was not significantly different b etween SU and ST cells. However, in the SU PP cells, glucose release was in creased compared with ST PP cells, both in the absence of glucagon (76.1 +/ - 4 vs. 54.8 +/- 3 nmol.h(-1).mg cell wet wt(-1)) and at all glucagon conce ntrations. In SU-fed PV cells, glucose release was increased compared with ST PV cells in the absence of glucagon (79.3 +/- 5 vs. 56.4 +/- 5 nmol.h(-1 ) . mg cell wet wt(-1)) and at low glucagon concentrations. Maximal glucose -6-phosphatase activity (in nmol.min(-1).mg protein(-1)) was elevated in SU compared with ST cells (61.4 +/- 3 vs. 37.5 +/- 4 in PP and 37.5 +/- 4 vs. 29.5 +/- 3 in PV cells). In contrast, maximal glucokinase activity (in nmo l . min(-1) . mg protein(-1)) was elevated in ST compared with SU cells (15 .9 +/- 2 vs. 12.1 +/- 1 in PP and 19.4 +/- 2 vs. 14.2 +/- 1 in PV cells). T hese data demonstrate that SU increases the capacity for glucose release in both PP and PV hepatocytes, in part because of reciprocal changes in gluco se-6-phosphatase and glucokinase.