Increased net hepatic glucose output from gluconeogenic precursors after high-sucrose diet feeding in male rats.

A high-sucrose diet reduces the ability of insulin to suppress hepatic glucose production (hepatic insulin resistance) in rats. The purpose of the present study was to investigate the contribution of hepatic gluconeogenesis to sucrose-induced hepatic insulin resistance. Single-pass liver perfusions were performed on 24-h food-deprived male Wistar rats after 8 wk on either a high-corn starch (ST; 68% of energy) or high-sucrose (SU; 68% of energy) diet. Hepatic glucose output (HGO, micromol of glucose x min(-1) x g(-1)) in the presence of lactate, alanine, or dihydroxyacetone (DHA) was used as an estimate of gluconeogenic capacity, because liver glycogen levels after the 24-h fast were negligible (<1.2 mg/g). HGO was significantly (P < 0.05) greater in SU vs. ST at all concentrations of lactate, alanine, and DHA. Maximal rates of HGO were 1.9 +/- 0.4 and 2.8 +/- 0.3 at 10 mM lactate, 0.6 +/- 0.2 and 1.4 +/- 0.3 at 10 mM alanine, and 1.7 +/- 0.3 and 2.6 +/- 0.2 at 20 mM DHA in ST and SU, respectively. When HGO was matched between SU and ST with the use of different precursor concentrations, there was a significant (P < 0.05) reduction in the ability of insulin (175 microU/ml) to suppress HGO in SU vs. ST. These data suggest that sucrose feeding increases gluconeogenesis from lactate, alanine, and DHA and that this route of glucose production is resistant to insulin suppression.