Thorburn A W, Gumbiner B, Brechtel G, Henry R R
Department of Medicine, University of California, San Diego.
Diabetes. 1990 Jan;39(1):22-30. doi: 10.2337/diacare.39.1.22.
Hyperinsulinemia and hyperglycemia per se both stimulate glucose uptake and the disposal of glucose by oxidative (Gox) and nonoxidative (Nox) metabolism. However, the intracellular metabolic fate of glucose may not be the same when glucose uptake is stimulated predominantly by either of these mechanisms due to different effects on fat oxidation (Fox). To address this issue, 11 healthy subjects each had four glucose-clamp studies performed in combination with indirect calorimetry to compare Gox, Nox, and Fox at two different rates of glucose uptake (approximately 7 and 10 mg.kg-1 fat-free mass [FFM].min-1) matched at each level by either hyperglycemia or hyperinsulinemia. When glucose uptake was matched at the lower rate (7 mg.kg-1 FFM.min-1), there was less suppression of both FFA (33 vs. 43%, P less than 0.05) and Fox (73 vs. 90%, P less than 0.05) and less stimulation of incremental (above basal) Gox (1.95 vs. 2.49 mg.kg-1 FFM.min-1, P less than 0.025) at low insulin (72 pM) and hyperglycemia (21.8 mM) compared with high insulin (280 pM) and euglycemia (5.1 mM). Matching glucose uptake at the higher rates (10 mg.kg-1 FFM.min-1) required greater than 300 pM of insulin (309 and 632 pM) in both studies and resulted in maximal suppression of FFA (49 vs. 46%, NS) and Fox (both greater than 90%, NS) and similar incremental Gox (2.89 vs. 2.73 mg.kg-1 FFM.min-1, NS) whether at hyperglycemia (15.7 mM) or euglycemia (5.2 mM). Therefore, both hyperinsulinemia and hyperglycemia stimulate glucose uptake and increase intracellular glucose availability, but insulin also regulates Gox by suppression of FFA and Fox. However, when FFA and Fox are maximally suppressed, the rate of glucose uptake, rather than the prevailing insulin level, determines the distribution of intracellular glucose metabolism.
高胰岛素血症和高血糖本身都会刺激葡萄糖摄取以及通过氧化代谢（Gox）和非氧化代谢（Nox）对葡萄糖的处置。然而，当葡萄糖摄取主要由这两种机制中的任何一种刺激时，由于对脂肪氧化（Fox）的影响不同，葡萄糖在细胞内的代谢命运可能并不相同。为了解决这个问题，11名健康受试者分别进行了四项葡萄糖钳夹研究，并结合间接测热法，以比较在两种不同葡萄糖摄取速率（约7和10mg·kg-1去脂体重[FFM]·min-1）下的Gox、Nox和Fox，每种速率在高血糖或高胰岛素血症状态下进行匹配。当葡萄糖摄取以较低速率（7mg·kg-1FFM·min-1）匹配时，与高胰岛素（280pM）和正常血糖（5.1mM）相比，在低胰岛素（72pM）和高血糖（21.8mM）状态下，游离脂肪酸（FFA）（33%对43%，P<0.05）和Fox（73%对90%，P<0.05）的抑制作用较小，增量（高于基础值）Gox的刺激作用也较小（1.95对2.49mg·kg-1FFM·min-1，P<0.025）。在两项研究中，以较高速率（10mg·kg-1FFM·min-1）匹配葡萄糖摄取需要大于300pM的胰岛素（309和632pM），并且无论在高血糖（15.7mM）还是正常血糖（5.2mM）状态下，都会导致FFA（49%对46%，无显著性差异）和Fox（均大于90%，无显著性差异）的最大抑制以及相似的增量Gox（2.89对2.73mg·kg-1FFM·min-1，无显著性差异）。因此，高胰岛素血症和高血糖均刺激葡萄糖摄取并增加细胞内葡萄糖可用性，但胰岛素也通过抑制FFA和Fox来调节Gox。然而，当FFA和Fox被最大程度抑制时，葡萄糖摄取速率而非当前的胰岛素水平决定了细胞内葡萄糖代谢的分布。
