Acute enhancement of insulin secretion by FFA in humans is lost with prolonged FFA elevation
Acute enhancement of insulin secretion by FFA in humans is lost with prolonged FFA elevation
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DOI：
10.1152/ajpendo.1999.276.6.e1055
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发表时间：
1999-06-01
影响因子：
5.1
通讯作者：
Lewis, GF
中科院分区：
文献类型：
--
作者：
Carpentier, A;Mittelman, SD;Lewis, GF
游离脂肪酸（FFA）升高对人体p细胞功能的体内影响仍然存在极大的争议。我们研究了在健康年轻男性中，血浆FFA与对照组相比约2倍升高对葡萄糖刺激的胰岛素分泌（GSIS）的急性（90分钟）和慢性（48小时）影响。研究了GSIS对分级静脉葡萄糖输注（峰值血糖，类似于10 mmol/l，n = 8）和两步高血糖钳夹（10和20 mmol/l，n = 8）的反应。在急性研究中，与对照组相比，GSIS显著更高，胰岛素敏感性指数（S-I）更低，并且处置指数（DI =胰岛素敏感性x胰岛素分泌）在FFA升高的情况下不变[2步钳夹：DI = 8.9 +/- 1.4 x 10（-3）l（2）。kg（-1）。对照组为10.0 +/- 1.9 x 10（-3）l（2）。kg（-1）。min（-2），高FFA，P =无显著性（NS）]。在慢性研究中，对照和高FFA研究之间的绝对GSIS没有差异，但是SI降低，并且如通过DI（2步钳夹：DI = 10.0 +/- 1.2 x 10（-3）l（2））评估的胰岛素分泌的预期代偿性增加丧失。kg（-1）。对照组为6.1 +/- 0.7 x 10（-3）l（2）。kg（-1）min（-2），FFA高，P = 0.01）。总之，1）急性和慢性FFA升高诱导胰岛素抵抗; 2）在急性FFA升高的情况下，这种胰岛素抵抗被FFA诱导的胰岛素分泌增加精确地抵消，使得DI不改变;和3）慢性FFA升高使这种β细胞补偿失效。
The in vivo effect of elevated free fatty acids (FFA) on p-cell function in humans remains extremely controversial. We examined, in healthy young men, the acute (90 min) and chronic (48 h) effects of an approximately twofold elevation of plasma FFA vs. control on glucose-stimulated insulin secretion (GSIS). GSIS was studied in response to a graded intravenous glucose infusion (peak plasma glucose, similar to 10 mmol/l, n = 8) and a two-step hyperglycemic clamp (10 and 20 mmol/l, n = 8). In the acute studies, GSIS was significantly higher, insulin sensitivity index (S-I) was lower, and disposition index (DI = insulin sensitivity x insulin secretion) was unchanged with elevated FFA vs. control [2-step clamp: DI = 8.9 +/- 1.4 x 10(-3) l(2) . kg(-1) . min(-2) in control vs. 10.0 +/- 1.9 x 10(-3) l(2). kg(-1) . min(-2) with high FFA, P = nonsignificant (NS)]. In the chronic studies, there was no difference in absolute GSIS between control and high FFA studies, but there was a reduction in SI and a loss of the expected compensatory increase in insulin secretion as assessed by the DI (2-step clamp: DI = 10.0 +/- 1.2 x 10(-3) l(2) . kg(-1) . min(-2) in control vs. 6.1 +/- 0.7 x 10(-3) l(2) . kg(-1) min(-2) with high FFA, P = 0.01). In summary, 1) acute and chronic FFA elevation induces insulin resistance; 2) with acute FFA elevation, this insulin resistance is precisely countered by an FFA-induced increase in insulin secretion, such that DI does not change; and 3) chronic FFA elevation disables this beta-cell compensation.