Journal
DIABETES
Volume 61, Issue 12, Pages 3156-3166Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db12-0418
Keywords
-
Categories
Funding
- National Institutes of Health General Clinical Research Center [RR-00036]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK-064811, DK-26356, DK-059739]
- Colorado Tobacco Research Program [3K-027]
Ask authors/readers for more resources
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 sensitiviy 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 second-hand smoke. Diabetes 61:3156-3166, 2012
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available