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游离脂肪酸诱导的外周胰岛素抵抗增强健康人的内脏葡萄糖摄取。

Free fatty acid-induced peripheral insulin resistance augments splanchnic glucose uptake in healthy humans.

作者信息

Bajaj Mandeep, Berria Rachele, Pratipanawatr Thongchai, Kashyap Sangeeta, Pratipanawatr Wilailak, Belfort Renata, Cusi Kenneth, Mandarino Lawrence, DeFronzo Ralph A

机构信息

Diabetes Division, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284, USA.

出版信息

Am J Physiol Endocrinol Metab. 2002 Aug;283(2):E346-52. doi: 10.1152/ajpendo.00329.2001.

DOI:10.1152/ajpendo.00329.2001
PMID:12110541
Abstract

To investigate the effect of elevated plasma free fatty acid (FFA) concentrations on splanchnic glucose uptake (SGU), we measured SGU in nine healthy subjects (age, 44 +/- 4 yr; body mass index, 27.4 +/- 1.2 kg/m(2); fasting plasma glucose, 5.2 +/- 0.1 mmol/l) during an Intralipid-heparin (LIP) infusion and during a saline (Sal) infusion. SGU was estimated by the oral glucose load (OGL)-insulin clamp method: subjects received a 7-h euglycemic insulin (100 mU x m(-2) x min(-1)) clamp, and a 75-g OGL was ingested 3 h after the insulin clamp was started. After glucose ingestion, the steady-state glucose infusion rate (GIR) during the insulin clamp was decreased to maintain euglycemia. SGU was calculated by subtracting the integrated decrease in GIR during the period after glucose ingestion from the ingested glucose load. [3-(3)H]glucose was infused during the initial 3 h of the insulin clamp to determine rates of endogenous glucose production (EGP) and glucose disappearance (R(d)). During the 3-h euglycemic insulin clamp before glucose ingestion, R(d) was decreased (8.8 +/- 0.5 vs. 7.6 +/- 0.5 mg x kg(-1) x min(-1), P < 0.01), and suppression of EGP was impaired (0.2 +/- 0.04 vs. 0.07 +/- 0.03 mg x kg(-1) x min(-1), P < 0.01). During the 4-h period after glucose ingestion, SGU was significantly increased during the LIP vs. Sal infusion study (30 +/- 2 vs. 20 +/- 2%, P < 0.005). In conclusion, an elevation in plasma FFA concentration impairs whole body glucose R(d) and insulin-mediated suppression of EGP in healthy subjects but augments SGU.

摘要

为研究血浆游离脂肪酸(FFA)浓度升高对内脏葡萄糖摄取(SGU)的影响,我们在9名健康受试者(年龄44±4岁;体重指数27.4±1.2kg/m²;空腹血糖5.2±0.1mmol/L)进行脂肪乳-肝素(LIP)输注和生理盐水(Sal)输注期间测量了SGU。SGU通过口服葡萄糖负荷(OGL)-胰岛素钳夹法估算:受试者接受7小时的正常血糖胰岛素(100mU·m⁻²·min⁻¹)钳夹,并在胰岛素钳夹开始3小时后摄入75g OGL。摄入葡萄糖后,胰岛素钳夹期间的稳态葡萄糖输注率(GIR)降低以维持正常血糖。SGU通过从摄入的葡萄糖负荷中减去摄入葡萄糖后期间GIR的综合降低值来计算。在胰岛素钳夹的最初3小时内输注[3-(³)H]葡萄糖以确定内源性葡萄糖生成(EGP)和葡萄糖消失率(R(d))。在摄入葡萄糖前的3小时正常血糖胰岛素钳夹期间,R(d)降低(8.8±0.5对7.6±0.5mg·kg⁻¹·min⁻¹,P<0.01),并且EGP的抑制受损(0.2±0.04对0.07±0.03mg·kg⁻¹·min⁻¹,P<0.01)。在摄入葡萄糖后的4小时期间,与Sal输注研究相比,LIP输注期间SGU显著增加(30±2对20±2%,P<0.005)。总之,血浆FFA浓度升高损害健康受试者的全身葡萄糖R(d)和胰岛素介导的EGP抑制,但增加SGU。

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