在健康人体中，非酯化脂肪酸（NEFA）的急性升高会导致高胰岛素血症，但对胰岛素分泌率没有影响。
Acute elevation of NEFA causes hyperinsulinemia without effect on insulin secretion rate in healthy human subjects.
作者信息
Balent Beate, Goswami Gayotri, Goodloe George, Rogatsky Eduard, Rauta Olimpia, Nezami Robert, Mints Lisa, Angeletti Ruth Hogue, Stein Daniel T
机构信息
Albert Einstein College of Medicine, Yeshiva University, Bronx, New York 10461, USA.
出版信息
Ann N Y Acad Sci. 2002 Jun;967:535-43. doi: 10.1111/j.1749-6632.2002.tb04313.x.
Increased circulating levels of nonesterified free fatty acids (NEFA) have been observed in such hyperinsulinemic states as obesity, impaired glucose tolerance, diabetes, and dyslipidemia where they have been causally linked to the development of insulin resistance and hyperinsulinemia. The concentration of NEFA in plasma is believed to have direct modifying effects on insulin secretion and clearance. It remains controversial whether acute increases in NEFA potentiate insulin secretion in human subjects. We studied the effect of an acute elevation of NEFA during lipid-heparin infusion compared to a glycerol-only control on glucose-stimulated insulin secretion and clearance during a 120-min hyperglycemic (10 mM) clamp in 7 healthy normoglucose-tolerant volunteers. The metabolic clearance rate of C-peptide (MCR(CP)) was measured in each subject during the study by simultaneous infusion of C-peptide. Insulin secretion rate (ISR) was calculated from deconvolution of C-peptide data after correction for the rate of C-peptide infusion. Clearance rate of insulin (MCR(INS)) was calculated based upon endogenous ISR. Plasma glucose (mg/dL): basal (90-115 min) 90.2 +/- 2.8 vs. 90.2 +/- 2.3; clamp (150-240 min) 180.5 +/- 2.8 vs. 180.9 +/- 1.3. Plasma insulin (pmol/L): prebasal (fasting) 29.6 +/- 10.0 vs. 29.8 +/- 10.6; basal (90-115 min) 30.1 +/- 9.2 vs. 34.5 +/- 12.1; second phase clamp (210-240 min) 127.6 +/- 18.2 vs. 182.5 +/- 17.3*. Plasma NEFA (mM): prebasal 0.47 +/- 0.08 vs. 0.52 +/- 0.09; basal 0.35 +/- 0.05 vs. 0.98 +/- 0.02*; clamp (122-240 min) 0.06 +/- 0.02 vs. 0.77 +/- 0.06*. ISR (pmol/min): prebasal 72.7 +/- 7.5 vs. 72.0 +/- 7.9; second phase clamp (210-240 min) 268.5 +/- 27.2 vs. 200.2 +/- 23.7. MCR(INS) (mL/min): prebasal 3393 +/- 488 vs. 3370 +/- 511; clamp 2284 +/- 505 vs. 1214 +/- 153* (*p < 0.05 glycerol vs. intralipid/heparin). This study demonstrates that acute NEFA elevation causes hyperinsulinemia due to a significant decrease in systemic insulin clearance without increasing rates of insulin secretion.
在肥胖、糖耐量受损、糖尿病和血脂异常等高胰岛素血症状态下，已观察到循环中游离脂肪酸（NEFA）水平升高，并且它们与胰岛素抵抗和高胰岛素血症的发生存在因果关系。血浆中NEFA的浓度被认为对胰岛素分泌和清除具有直接调节作用。急性升高NEFA是否能增强人类受试者的胰岛素分泌仍存在争议。我们研究了在7名健康糖耐量正常的志愿者中，与仅输注甘油的对照组相比，脂质 - 肝素输注期间NEFA急性升高对120分钟高血糖（10 mM）钳夹期间葡萄糖刺激的胰岛素分泌和清除的影响。在研究过程中，通过同时输注C肽来测量每个受试者的C肽代谢清除率（MCR(CP)）。胰岛素分泌率（ISR）通过对C肽输注速率进行校正后对C肽数据进行反卷积计算得出。胰岛素清除率（MCR(INS)）基于内源性ISR进行计算。血浆葡萄糖（mg/dL）：基础值（90 - 115分钟）90.2±2.8 vs. 90.2±2.3；钳夹期（150 - 240分钟）180.5±2.8 vs. 180.9±1.3。血浆胰岛素（pmol/L）：基础前（空腹）29.6±10.0 vs. 29.8±10.6；基础值（90 - 115分钟）30.1±9.2 vs. 34.5±12.1；钳夹期第二阶段（210 - 240分钟）127.6±18.2 vs. 182.5±17.3*。血浆NEFA（mM）：基础前0.47±0.08 vs. 0.52±0.09；基础值0.35±0.05 vs. 0.98±0.02*；钳夹期（122 - 240分钟）0.06±0.02 vs. 0.77±0.06*。ISR（pmol/min）：基础前72.7±7.5 vs. 72.0±7.9；钳夹期第二阶段（210 - 240分钟）268.5±27.2 vs. 200.2±23.7。MCR(INS)（mL/min）：基础前3393±488 vs. 3370±511；钳夹期2284±505 vs. 1214±153*（*甘油组与脂质/肝素组相比，p < 0.05）。本研究表明，急性NEFA升高导致高胰岛素血症是由于全身胰岛素清除率显著降低，而不是胰岛素分泌速率增加。
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