Glucose transport and metabolism in rat renal proximal tubules: multicomponent effects of insulin.

Glucose transport and metabolism in rat renal proximal tubules: multicomponent effects of insulin.
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大鼠肾近曲小管中的葡萄糖转运和代谢:胰岛素的多组分效应。

DOI:
10.1016/0005-2736(86)90146-x
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发表时间:
1986
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
McAvoy,EM
McAvoy,EM
中科院分区:
--
文献类型:
--
作者:
Kleinzeller,A;McAvoy,EM

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使用富含近端成分的大鼠肾小管悬浮液研究了葡萄糖转运和代谢以及胰岛素对其的影响。(1)[U-14 C]葡萄糖氧化是一个可饱和过程(K m 3.1±0.2 mM;V max 14±0.2 μmole 14 CO 2 形成/g组织蛋白每小时。)葡萄糖氧化和由葡萄糖形成[ 14 C]乳酸被部分抑制根皮苷和根皮素:数据表明,葡萄糖进入细胞代谢库的限速是由钠-葡萄糖协同转运系统(在刷状缘)和平衡、根皮素敏感系统(在基底侧膜)发生的。将外部葡萄糖从 5 mM 提高到 30 mM 会显着增加需氧和无氧乳酸的形成。乳酸的糖异生不受葡萄糖浓度变化的影响。(2)链脲佐菌素给药24小时后,有氧乳酸形成增强,小管对甲基α-d-葡萄糖苷的摄取增强,而无氧糖酵解减弱。链脲佐菌素处理 (ST) 会增加葡萄糖氧化的 K m 和 V max ;糖异生和乳酸氧化不受影响。链脲佐菌素处理对乳酸形成的影响被1 mU/ml胰岛素消除。(3)链脲佐菌素处理增加组织己糖激酶活性,降低葡萄糖-6-磷酸酶,但对果糖-1, 6-二磷酸酶、磷酸烯醇丙酮酸羧激酶和丙酮酸脱氢酶无显着影响。数据表明链脲佐菌素诱导碳水化合物代谢细胞酶发生快速变化。(4)链脲佐菌素对甲基α-葡萄糖苷摄取的增强作用是短暂的:给药后8天,与对照组没有发现显着差异。(5)得出的结论是,在给定的实验条件下,胰岛素增强了基底侧膜根皮素敏感途径的平衡葡萄糖进入,并暂时抑制Na-葡萄糖协同运输系统。
Glucose transport and metabolism, and the effect of insulin thereon, was studied using suspensions of rat renal tubules enriched in the proximal component.(1)[U-14 C] Glucose oxidation is a saturable process (K m 3.1±0.2 mM; V max 14±0.2 μmole 14 CO 2 formed/g tissue protein per h.) Glucose oxidation and [14 C] lactate formation from glucose are inhibited in part by phlorizin and phloretin: the data suggest that the rate-limiting entry of glucose into the cell metabolic pool occurs by both the Na-glucose cotransport system (at the brush border) and the equilibrating, phloretin-sensitive system (at the basal-lateral membrane). Raising external glucose from 5 to 30 mM markedly increases aerobic and anaerobic lactate formation. Gluconeogenesis from lactate is not affected by variations of glucose concentrations.(2) 24 h after streptozotocin administration, aerobic lactate formation is enhanced, as is the uptake of methyl α-d-glucoside by the tubules, while anaerobic glycolysis is depressed. Streptozotocin treatment (ST) increases both the K m and V max of glucose oxidation; gluconeogenesis and lactate oxidation are not affected. The effect of streptozotocin treatment on lactate formation are abolished by 1 mU/ml insulin.(3) Streptozotocin treatment increases tissue hexokinase activity, decreases glucose-6-phosphatase, but has no significant effect on fructose-1, 6-diphosphatase, phosphoenolpyruvate carboxykinase and pyruvate dehydrogenase. The data demonstrate fast streptozotocin-induced changes in cellular enzymes of carbohydrate metabolism.(4) The enhancing effect of streptozotocin on methyl α-glucoside uptake is transient: 8 days after administration of the agent, no significant difference from controls is found.(5) It is concluded that under the given experimental conditions insulin enhances the equilibrating glucose entry by the phloretin-sensitive pathway at the basal-lateral membrane, and transiently inhibits the Na-glucose cotransport system.