Diabetes 2012,
PMID: 22966072
Bergman, Bryan C; Perreault, Leigh; Hunerdosse, Devon; Kerege, Anna; Playdon, Mary; Samek, Ali M; Eckel, Robert H
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-1(ser636) phosphorylation. In muscle cell culture, nicotine exposure significantly increased IRS-1(ser636) phosphorylation and decreased insulin sensitivity, recapitulating the phenotype of smoking-induced insulin resistance in humans. The two pathways known to stimulate IRS-1(ser636) 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-1(ser636) 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.
Diseases/Pathways annotated by Medline MESH: Insulin Resistance
Document information provided by NCBI PubMed
Text Mining Data
IRS-1 ⊣ p44/42: "
Inhibition of mTOR, but not
p44/42 MAPK, during nicotine exposure
prevented IRS-1 ( ser636 ) phosphorylation and normalized insulin sensitivity
"
IRS-1 ⊣ MAPK: "
Inhibition of mTOR, but not p44/42 MAPK , during nicotine exposure prevented IRS-1 ( ser636 ) phosphorylation and normalized insulin sensitivity
"
IRS-1 ⊣ p44/42 MAPK: "
Inhibition of mTOR, but not p44/42 MAPK , during nicotine exposure prevented IRS-1 ( ser636 ) phosphorylation and normalized insulin sensitivity
"
IRS-1 → mTOR: "
Inhibition of mTOR , but not p44/42 MAPK, during nicotine exposure prevented IRS-1 ( ser636 ) phosphorylation and normalized insulin sensitivity
"
Manually curated Databases
No curated data.