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正常人在游离脂肪酸刺激的糖异生过程中肝脏自身调节的体内证据。

In vivo evidence for hepatic autoregulation during FFA-stimulated gluconeogenesis in normal humans.

作者信息

Clore J N, Glickman P S, Nestler J E, Blackard W G

机构信息

Division of Endocrinology and Metabolism, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0111.

出版信息

Am J Physiol. 1991 Oct;261(4 Pt 1):E425-9. doi: 10.1152/ajpendo.1991.261.4.E425.

DOI:10.1152/ajpendo.1991.261.4.E425
PMID:1928334
Abstract

To examine the effect of increased gluconeogenesis [by increasing free fatty acids (FFA)] on hepatic glucose output (HGO) and on the first substrate (glucose) cycle, a primed continuous infusion of [2-3H]- and [6-14C]glucose was infused to isotopic steady state in 12 normal male volunteers after an overnight fast. Blood samples for the determination of glucose specific activity were obtained before and after an infusion of saline (n = 6) or 10% Intralipid and heparin (90 mU.kg-1.min-1, n = 6). Plasma FFA (593.3 +/- 74.5 to 971.1 +/- 127.1 mumol/l, P = 0.007) and glycerol (68.0 +/- 5.9 vs. 222.4 +/- 32.0 mumol/l, P = 0.002) increased during the lipid infusion, and beta-hydroxybutyrate levels rose from 0.24 +/- 0.12 to 0.50 +/- 0.17 mmol/l (P = 0.01). No change in plasma glucose, insulin, or glucagon levels was observed during the study, and levels of the gluconeogenic substrates alanine and lactate were also unchanged. Baseline rates of glucose cycling (rate of appearance of [2-3H]glucose minus rate of appearance of [6-14C]glucose) were similar in the two groups [1.44 +/- 0.33 vs. 1.33 +/- 0.44 mumol.kg-1.min-1, not significant (NS)] and did not change during either saline or lipid infusion, respectively. However, Cori cycle activity (the conversion of [6-14C]- to [1-14C]glucose) increased significantly from 0.59 +/- 0.19 to 1.28 +/- 0.19 mumol.kg-1.min-1 (P = 0.002) after FFA and glycerol levels had been increased, in marked contrast to the saline control (0.51 +/- 0.18 to 0.39 +/- 0.18 mumol.kg-1.min-1, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

为了研究增加糖异生作用(通过增加游离脂肪酸[FFA])对肝脏葡萄糖输出(HGO)和首个底物(葡萄糖)循环的影响,在12名正常男性志愿者过夜禁食后,以初量持续输注法输注[2-³H]-和[6-¹⁴C]葡萄糖直至同位素稳态。在输注生理盐水(n = 6)或10%英脱利匹特和肝素(90 mU·kg⁻¹·min⁻¹,n = 6)之前和之后采集血样以测定葡萄糖比活性。脂质输注期间,血浆FFA(593.3±74.5至971.1±127.1 μmol/l,P = 0.007)和甘油(68.0±5.9对222.4±32.0 μmol/l,P = 0.002)升高,β-羟丁酸水平从0.24±0.12升至0.50±0.17 mmol/l(P = 0.01)。研究期间未观察到血浆葡萄糖、胰岛素或胰高血糖素水平的变化,糖异生底物丙氨酸和乳酸水平也未改变。两组的葡萄糖循环基线速率([2-³H]葡萄糖的出现速率减去[6-¹⁴C]葡萄糖的出现速率)相似[1.44±0.33对1.33±0.44 μmol·kg⁻¹·min⁻¹,无显著差异(NS)],且在输注生理盐水或脂质期间均未改变。然而,在FFA和甘油水平升高后,科里循环活性([6-¹⁴C]-葡萄糖向[1-¹⁴C]葡萄糖的转化)从0.59±0.19显著增加至1.28±0.19 μmol·kg⁻¹·min⁻¹(P = 0.002),这与生理盐水对照组(0.51±0.18至0.39±0.18 μmol·kg⁻¹·min⁻¹,NS)形成显著对比。(摘要截取自250字)

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