Effects of insulin on the metabolic control of hepatic gluconeogenesis in vivo.
Effects of insulin on the metabolic control of hepatic gluconeogenesis in vivo.
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DOI：
10.2337/db09-0328
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发表时间：
2009-12
期刊：
影响因子：
7.7
通讯作者：
Cherrington AD
中科院分区：
文献类型：
--
作者：
Edgerton DS;Ramnanan CJ;Grueter CA;Johnson KM;Lautz M;Neal DW;Williams PE;Cherrington AD
胰岛素在mRNA水平上抑制致瘤基因的表达，但该激素在体内似乎仅具有弱的抑制作用。本研究的目的是：1）确定胰岛素的最大生理作用，2）确定其对促血管生成调节位点作用的相对重要性，3）将这些变化与细胞水平的改变相关联。在5小时正葡萄糖钳夹期间，在三种胰岛素水平（接近基础、4倍或16倍）下研究清醒60小时禁食犬。使用生长抑素联合门静脉胰岛素和胰高血糖素输注控制胰腺激素。使用动静脉差分技术评估葡萄糖代谢，并评估分子信号。胰岛素降低了葡萄糖-6-磷酸（G6 P）的促血管生成通量，但仅在接近最大生理水平（16×基础）时。与其对净肝糖原分解的抑制作用相比，这种作用是适度的，发生在30分钟内，并且与肝脂肪氧化的显著降低、肝果糖2，6-二磷酸水平的增加以及乳酸、甘油和氨基酸提取的减少相关。在研究的剩余4.5小时内，尽管PEPCK含量显著降低，但G6 P的致炎通量未进一步减少，表明该酶在犬致炎调节中的控制强度较差。高胰岛素水平可迅速抑制犬的葡萄糖异生流。最初减少肝脏乳酸提取是重要的，后来减少的促血管生成前体的可用性发挥作用。PEPCK的变化似乎很少或根本没有急性影响的产热通量。
Insulin represses the expression of gluconeogenic genes at the mRNA level, but the hormone appears to have only weak inhibitory effects in vivo. The aims of this study were 1) to determine the maximal physiologic effect of insulin, 2) to determine the relative importance of its effects on gluconeogenic regulatory sites, and 3) to correlate those changes with alterations at the cellular level. Conscious 60-h fasted canines were studied at three insulin levels (near basal, 4×, or 16×) during a 5-h euglycemic clamp. Pancreatic hormones were controlled using somatostatin with portal insulin and glucagon infusions. Glucose metabolism was assessed using the arteriovenous difference technique, and molecular signals were assessed. Insulin reduced gluconeogenic flux to glucose-6-phosphate (G6P) but only at the near-maximal physiological level (16× basal). The effect was modest compared with its inhibitory effect on net hepatic glycogenolysis, occurred within 30 min, and was associated with a marked decrease in hepatic fat oxidation, increased liver fructose 2,6-bisphosphate level, and reductions in lactate, glycerol, and amino acid extraction. No further diminution in gluconeogenic flux to G6P occurred over the remaining 4.5 h of the study, despite a marked decrease in PEPCK content, suggesting poor control strength for this enzyme in gluconeogenic regulation in canines. Gluconeogenic flux can be rapidly inhibited by high insulin levels in canines. Initially decreased hepatic lactate extraction is important, and later reduced gluconeogenic precursor availability plays a role. Changes in PEPCK appear to have little or no acute effect on gluconeogenic flux.
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影响因子：
7.7
作者：
Boden, G;Chen, XH;Mozzoli, M
通讯作者：
Mozzoli, M
影响因子：
7.7
作者：
Boden, G;Cheung, P;Homko, C
通讯作者：
Homko, C
DOI：
10.1152/ajpendo.00320.2002
发表时间：
2002-11-01
影响因子：
5.1
作者：
Goldstein, RE;Rossetti, L;Cherrington, AD
通讯作者：
Cherrington, AD
影响因子：
29
作者：
Burgess, Shawn C.;He, TianTeng;Magnuson, Mark A.
通讯作者：
Magnuson, Mark A.
DOI：
10.1152/ajpendo.00136.2001
发表时间：
2002-02-01
影响因子：
5.1
作者：
Chu, CA;Sherck, SM;Cherrington, AD
通讯作者：
Cherrington, AD