Mechanisms of insulin resistance after insulin-induced hypoglycemia in humans: the role of lipolysis.
Mechanisms of insulin resistance after insulin-induced hypoglycemia in humans: the role of lipolysis.
复制标题
人类胰岛素引起低血糖后胰岛素抵抗的机制：脂肪分解的作用。
DOI：
10.2337/db09-0745
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发表时间：
2010-06
期刊：
影响因子：
7.7
通讯作者：
Fanelli, Carmine G.
中科院分区：
文献类型：
--
作者：
Lucidi, Paola;Rossetti, Paolo;Porcellati, Francesca;Pampanelli, Simone;Candeloro, Paola;Andreoli, Anna Marinelli;Perriello, Gabriele;Bolli, Geremia B.;Fanelli, Carmine G.
反调节期间发生的葡萄糖代谢变化部分是由血浆游离脂肪酸（FFA）增加介导的，这是低血糖激活脂肪分解的结果。然而，尚不清楚 FFA 是否也在低血糖后胰岛素抵抗的发展中发挥作用。我们使用阿昔莫司（一种脂解抑制剂）对八名健康志愿者进行了一系列研究。从下午 5:00 开始，在 2 小时高胰岛素正常血糖钳夹（血浆葡萄糖 [PG] 5.1 mmo/l）期间测量胰岛素作用。至晚上 7:00或在早晨 3 小时高胰岛素血糖钳夹（上午 10 点至下午 1:00）后，血糖正常（研究 1）或血糖降低（PG 3.2 mmol/l，研究 2-4），在此期间允许 FFA 水平增加（研究 2），用阿昔莫司抑制（研究 3），或用输注脂质代替（研究 4）。注入[6,6-2H2]-葡萄糖以测量葡萄糖通量。血浆肾上腺素、去甲肾上腺素、生长激素和皮质醇水平未发生变化（P > 0.2）。研究 2 与研究 1 相比，正常血糖钳夹期间的葡萄糖输注率 (GIR) 因早晨低血糖而降低（分别为 16.8 ± 2.3 与 34.1 ± 2.2 μmol/kg/min，P < 0.001）。研究 3 中低血糖期间的脂解作用被阻断，该效应在很大程度上被消除（28.9 ± 2.6 μmol/kg/min，与研究 1 相比，P > 0.2），并且在研究 4 中通过替代 FFA 很大程度上重现了该效应（22.3 ± 2.8 μmol/kg/min，P < 0.03 与研究 1 相比）。与研究2相比，研究3中的脂解阻断减少了内源性葡萄糖产生（2±0.3 vs. 0.85±0.1μmol/kg/min，P < 0.05）并增加了葡萄糖利用率（16.9±1.85 vs. 28.5±2.7 μmol/kg/min，P < 0.05）。在研究 4 中，GIR 下降约 23%（22.3 ± 2.8 μmol/kg/min，与研究 3 相比，P = 0.058），表明阿西莫司本身对胰岛素作用的作用。低血糖反调节引起的脂肪分解很大程度上介导了健康受试者的低血糖后胰岛素抵抗，估计总体贡献约为 39%。
Changes in glucose metabolism occurring during counterregulation are, in part, mediated by increased plasma free fatty acids (FFAs), as a result of hypoglycemia-activated lipolysis. However, it is not known whether FFA plays a role in the development of posthypoglycemic insulin resistance as well. We conducted a series of studies in eight healthy volunteers using acipimox, an inhibitor of lipolysis. Insulin action was measured during a 2-h hyperinsulinemic-euglycemic clamp (plasma glucose [PG] 5.1 mmo/l) from 5:00 p.m. to 7:00 p.m. or after a 3-h morning hyperinsulinemic-glucose clamp (from 10 a.m. to 1:00 p.m.), either euglycemic (study 1) or hypoglycemic (PG 3.2 mmol/l, studies 2–4), during which FFA levels were allowed to increase (study 2), were suppressed by acipimox (study 3), or were replaced by infusing lipids (study 4). [6,6-2H2]-Glucose was infused to measure glucose fluxes. Plasma adrenaline, norepinephrine, growth hormone, and cortisol levels were unchanged (P > 0.2). Glucose infusion rates (GIRs) during the euglycemic clamp were reduced by morning hypoglycemia in study 2 versus study 1 (16.8 ± 2.3 vs. 34.1 ± 2.2 μmol/kg/min, respectively, P < 0.001). The effect was largely removed by blockade of lipolysis during hypoglycemia in study 3 (28.9 ± 2.6 μmol/kg/min, P > 0.2 vs. study 1) and largely reproduced by replacement of FFA in study 4 (22.3 ± 2.8 μmol/kg/min, P < 0.03 vs. study 1). Compared with study 2, blockade of lipolysis in study 3 decreased endogenous glucose production (2 ± 0.3 vs. 0.85 ± 0.1 μmol/kg/min, P < 0.05) and increased glucose utilization (16.9 ± 1.85 vs. 28.5 ± 2.7 μmol/kg/min, P < 0.05). In study 4, GIR fell by ∼23% (22.3 ± 2.8 μmol/kg/min, vs. study 3, P = 0.058), indicating a role of acipimox per se on insulin action. Lipolysis induced by hypoglycemia counterregulation largely mediates posthypoglycemic insulin resistance in healthy subjects, with an estimated overall contribution of ∼39%.
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影响因子：
15.9
作者：
FANELLI, CG;DEFEO, P;BOLLI, GB
通讯作者：
BOLLI, GB
影响因子：
158.5
作者：
Gerstein, Hertzel C.;Miller, Michael E.;Friedewald, William T.
通讯作者：
Friedewald, William T.
影响因子：
6.7
作者：
FUCCELLA, LM;GOLDANIGA, G;SIRTORI, CR
通讯作者：
SIRTORI, CR
影响因子：
7.7
作者：
HELLER, SR;CRYER, PE
通讯作者：
CRYER, PE
DOI：
10.1016/s0889-8529(05)70083-9
发表时间：
1999-09-01
影响因子：
4.5
作者：
Bolli, GB;Fanelli, CG
通讯作者：
Fanelli, CG