IMPACT OF VARIABLE INSULINEMIA AND GLYCEMIA ON IN-VIVO GLYCOLYSIS ANDGLUCOSE STORAGE IN DOGS

To determine the impact of variable plasma insulin concentrations and glycemia on the partitioning of whole body glucose metabolism between glycolysis and glucose storage, we estimated endogenous hepatic glucos e production and rates of in vivo glycolytic flux (GF) and glucose sto rage (GS) in six normal dogs from the generation of plasma tritiated w ater ((H2O)-H-3) and [3-H-3]glucose specific activity during 150 min o f somatostatin euglycemic (E) and hyperglycemic (H) clamps at hypoinsu linemic, basal, intermediate, and high insulin levels. During both E a nd H clamps, overall rates of GF and GS increased with the rising insu lin levels, but the relative contributions to in vivo glucose disposal of GF decreased, whereas GS rose progressively with increasing insuli n levels. The relative contribution of GS during H to overall glucose disposal was greater at the lower insulin level. In addition, in absol ute terms, GF and GS were significantly higher (P < 0.05) during H tha n during E at all insulin levels. Moreover, the incremental rise in GF induced by H was equal for the low to intermediate insulin levels tes ted, independent of the prevailing free fatty acid (FFA) levels. Howev er, when whole body glucose disposal rates were matched, GF and GS rat es were independent of the coexisting glycemia, insulin, and/or FFA le vels. We conclude that 1) insulin has a major impact on the intracellu lar fate of infused glucose, with a lesser but significant effect of h yperglycemia per se on these processes; 2) the magnitude of the hyperg lycemia-induced increase in GF is independent of the prevailing insuli n level from low to intermediate levels; and 3) in vivo GF and GS are dependent on the net rate of glucose uptake into cells but independent of absolute FFA levels or whether glucose uptake is stimulated by rai sed insulin or glucose levels.