Novel and reversible mechanisms of smoking-induced insulin resistance in humans.
Novel and reversible mechanisms of smoking-induced insulin resistance in humans.
复制标题
吸烟引起的人类胰岛素抵抗的新颖和可逆机制。
作者：
Bergman BC;Perreault L;Hunerdosse D;Kerege A;Playdon M;Samek AM;Eckel RH
在美国，吸烟是可预防的发病率和死亡率的最常见原因，部分原因是它是胰岛素抵抗和2型糖尿病发展的独立危险因素。然而，吸烟诱导的胰岛素抵抗的机制尚不清楚。在这项研究中，我们发现与对照组相比，吸烟者的胰岛素敏感性较低，在戒烟1或2周后增加。戒烟后胰岛素敏感性的改善与IRS-1 ser 636磷酸化的正常化有关。在肌肉细胞培养中，尼古丁暴露显著增加IRS-1 ser 636磷酸化，降低胰岛素敏感性，重现了人类吸烟诱导的胰岛素抵抗的表型。已知刺激IRS-1 ser 636磷酸化的两种途径（p44/42丝裂原活化蛋白激酶[MAPK]和哺乳动物雷帕霉素靶蛋白[mTOR]）均受到尼古丁刺激。在尼古丁暴露期间，抑制mTOR而不是p44/42 MAPK可阻止IRS-1 ser 636磷酸化和正常化胰岛素敏感性。这些数据表明尼古丁通过激活mTOR诱导骨骼肌中的胰岛素抵抗。设计用于对抗骨骼肌mTOR激活的治疗剂可以预防无法戒烟或长期暴露于二手烟的人的胰岛素抵抗。
Smoking is the most common cause of preventable morbidity and mortality in the United States, in part because it is an independent risk factor for the development of insulin resistance and type 2 diabetes. However, mechanisms responsible for smoking-induced insulin resistance are unclear. In this study, we found smokers were less insulin sensitive compared with controls, which increased after either 1 or 2 weeks of smoking cessation. Improvements in insulin sensitivity after smoking cessation occurred with normalization of IRS-1ser636 phosphorylation. In muscle cell culture, nicotine exposure significantly increased IRS-1ser636 phosphorylation and decreased insulin sensitivity, recapitulating the phenotype of smoking-induced insulin resistance in humans. The two pathways known to stimulate IRS-1ser636 phosphorylation (p44/42 mitogen-activated protein kinase [MAPK] and mammalian target of rapamycin [mTOR]) were both stimulated by nicotine in culture. Inhibition of mTOR, but not p44/42 MAPK, during nicotine exposure prevented IRS-1ser636 phosphorylation and normalized insulin sensitivity. These data indicate nicotine induces insulin resistance in skeletal muscle by activating mTOR. Therapeutic agents designed to oppose skeletal muscle mTOR activation may prevent insulin resistance in humans who are unable to stop smoking or are chronically exposed to secondhand smoke.
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影响因子：
5.4
作者：
Boston, Ray C;Stefanovski, Darko;Bergman, Richard N
通讯作者：
Bergman, Richard N
DOI：
10.1046/j.1365-2362.1997.1330680.x
发表时间：
1997-05-01
影响因子：
5.5
作者：
Eliasson, B;Attvall, S;Smith, U
通讯作者：
Smith, U
影响因子：
5
作者：
FESKENS, EJM;KROMHOUT, D
通讯作者：
KROMHOUT, D
影响因子：
15.9
作者：
HELLERSTEIN, MK;BENOWITZ, NL;FAIX, D
通讯作者：
FAIX, D
DOI：
10.1161/01.atv.14.12.1946
发表时间：
1994-12-01
期刊：
ARTERIOSCLEROSIS AND THROMBOSIS
影响因子：
--
作者：
ELIASSON, B;ATTVALL, S;SMITH, U
通讯作者：
SMITH, U