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 gl uconeogenesis to sucrose-induced hepatic insulin resistance. Single-pa ss liver perfusions were performed on 24-h food-deprived male Wistar r ats after 8 wk on either a high-corn starch (ST; 68% of energy) or hig h-sucrose (SU; 68% of energy) diet. Hepatic glucose output (HGO, pmol of glucose . min(-1) . g(-1)) in the presence of lactate, alanine, or dihydroxyacetone (DHA) was used as an estimate of gluconeogenic capaci ty, 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 DH A in ST and SU, respectively. When HGO was matched between SU and ST w ith the use of different precursor concentrations, there was a signifi cant (P < 0.05) reduction in the ability of insulin (175 mu U/ml) to s uppress HGO in SU vs. ST. These data suggest that sucrose feeding incr eases gluconeogenesis from lactate, alanine, and DHA and that this rou te of glucose production is resistant to insulin suppression.