Vidal H, Comte B, Beylot M, Riou J P
Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine Alexis Carrel, Lyon, France.
J Biol Chem. 1988 Jul 5;263(19):9206-11.
Glucose metabolism and its hormonal regulation have been investigated in isolated enterocytes from rat small intestine. About 70% of the glucose consumed by the cells was transformed into lactate, 5% into pyruvate, and 4% into alanine. The remaining 20% was oxidized. Among several tested gastrointestinal peptides and hormones, only vasoactive intestinal peptide (VIP) was found to affect the metabolic fate of glucose. VIP (10(-7) M) induced a 40% inhibition of glucose oxidation without significant modification of either glucose uptake or production of lactate, pyruvate, and alanine. This acute inhibition was dose-dependent (Ki = 3.10(-11) M) and appeared to be dependent on the stimulation of cAMP production (K0.5 = 3.10(-9) M) since dibutyryl-cAMP and forskolin reproduced all the effects of VIP. Similar inhibition of cell respiration by VIP was observed when pyruvate, fructose, and dihydroxyacetone were used as substrates, while the oxidation of glutamine, ketone bodies, and octanoate was unaffected, suggesting that the peptide acts on pyruvate metabolism. The suppression of VIP effects by dichloroacetate (5 mM) and pyruvate (10 mM) and the significant decrease (18%) of the activity of the pyruvate dehydrogenase complex after incubation of the cells with the neuropeptide, support the hypothesis that the effects of VIP on glucose oxidation may occur through an inhibition of the pyruvate dehydrogenase complex. The total suppression of the inhibitory effects of VIP by sodium 2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate, a potent inhibitor of long-chain fatty acid oxidation, suggests that VIP did not affect the pyruvate dehydrogenase directly, but more probably acted through modifications of fatty acid oxidation.
已对大鼠小肠分离肠上皮细胞中的葡萄糖代谢及其激素调节进行了研究。细胞消耗的葡萄糖约70%转化为乳酸，5%转化为丙酮酸，4%转化为丙氨酸。其余20%被氧化。在几种经测试的胃肠肽和激素中，仅发现血管活性肠肽（VIP）会影响葡萄糖的代谢命运。VIP（10⁻⁷ M）可导致葡萄糖氧化受到40%的抑制，而葡萄糖摄取或乳酸、丙酮酸及丙氨酸的生成均无显著改变。这种急性抑制呈剂量依赖性（Ki = 3.10⁻¹¹ M），且似乎依赖于cAMP生成的刺激（K0.5 = 3.10⁻⁹ M），因为二丁酰-cAMP和福斯可林可重现VIP的所有作用。当使用丙酮酸、果糖和二羟基丙酮作为底物时，观察到VIP对细胞呼吸有类似的抑制作用，而谷氨酰胺、酮体和辛酸的氧化未受影响，这表明该肽作用于丙酮酸代谢。二氯乙酸盐（5 mM）和丙酮酸（10 mM）可抑制VIP的作用，且细胞与该神经肽孵育后丙酮酸脱氢酶复合体的活性显著降低（18%），这支持了VIP对葡萄糖氧化的作用可能通过抑制丙酮酸脱氢酶复合体而发生的假说。2-[6-(4-氯苯氧基)己基]环氧乙烷-2-羧酸钠是一种强效的长链脂肪酸氧化抑制剂，它可完全抑制VIP的抑制作用，这表明VIP并非直接影响丙酮酸脱氢酶，而更可能是通过改变脂肪酸氧化起作用。
