Christopher M J, Rantzau C, Ward G M, Alford F P
Department of Endocrinology, St. Vincent's Hospital, Fitzroy, Victoria, Australia.
Am J Physiol. 1994 Jan;266(1 Pt 1):E62-71. doi: 10.1152/ajpendo.1994.266.1.E62.
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 glucose production and rates of in vivo glycolytic flux (GF) and glucose storage (GS) in six normal dogs from the generation of plasma tritiated water (3H2O) and [3-3H]glucose specific activity during 150 min of somatostatin euglycemic (E) and hyperglycemic (H) clamps at hypoinsulinemic, basal, intermediate, and high insulin levels. During both E and H clamps, overall rates of GF and GS increased with the rising insulin levels, but the relative contributions to in vivo glucose disposal of GF decreased, whereas GS rose progressively with increasing insulin levels. The relative contribution of GS during H to overall glucose disposal was greater at the lower insulin level. In addition, in absolute terms, GF and GS were significantly higher (P < 0.05) during H than during E at all insulin levels. Moreover, the incremental rise in GF induced by H was equal for the low to intermediate insulin levels tested, independent of the prevailing free fatty acid (FFA) levels. However, when whole body glucose disposal rates were matched, GF and GS rates were independent of the coexisting glycemia, insulin, and/or FFA levels. We conclude that 1) insulin has a major impact on the intracellular fate of infused glucose, with a lesser but significant effect of hyperglycemia per se on these processes; 2) the magnitude of the hyperglycemia-induced increase in GF is independent of the prevailing insulin 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 raised insulin or glucose levels.
为了确定血浆胰岛素浓度和血糖变化对全身葡萄糖代谢在糖酵解和葡萄糖储存之间分配的影响，我们在六只正常犬中，通过在150分钟的生长抑素维持血糖正常（E）和高血糖（H）钳夹实验中，分别处于低胰岛素、基础、中等和高胰岛素水平时，测定血浆氚水（3H2O）和[3-3H]葡萄糖比活性，估算了内源性肝葡萄糖生成以及体内糖酵解通量（GF）和葡萄糖储存（GS）速率。在E钳夹和H钳夹期间，GF和GS的总体速率均随胰岛素水平升高而增加，但GF对体内葡萄糖处置的相对贡献降低，而GS则随胰岛素水平升高而逐渐增加。在较低胰岛素水平时，H期间GS对总体葡萄糖处置的相对贡献更大。此外，从绝对值来看，在所有胰岛素水平下，H期间的GF和GS均显著高于E期间（P < 0.05）。而且，在低至中等胰岛素水平测试中，H诱导的GF增量上升是相等的，与当时的游离脂肪酸（FFA）水平无关。然而，当全身葡萄糖处置速率相匹配时，GF和GS速率与同时存在的血糖、胰岛素和/或FFA水平无关。我们得出以下结论：1）胰岛素对输注葡萄糖的细胞内命运有主要影响，高血糖本身对这些过程也有较小但显著的影响；2）高血糖诱导的GF增加幅度在低至中等水平时与当时的胰岛素水平无关；3）体内GF和GS取决于葡萄糖进入细胞的净速率，但与绝对FFA水平或葡萄糖摄取是由升高的胰岛素还是葡萄糖水平刺激无关。
