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. Author manuscript; available in PMC: 2016 Sep 13.
Published in final edited form as: Nat Rev Endocrinol. 2016 Mar 4;12(5):299–308. doi: 10.1038/nrendo.2016.32

Figure 2. Mechanisms by which nicotine leads to insulin resistance.

Figure 2

Nicotine inhibits hypothalamic 5´-AMP-activated protein kinase (AMPK) activity, decreases food intake and increases thermogenesis. Nicotine also enhances lipolysis and increases the delivery of free fatty acids (FFA) to the liver and skeletal muscle. These effects of nicotine are associated with increased hepatic secretion of VLDL cholesterol and intramyocellular lipid saturation, as well as peripheral insulin resistance. Nicotine increases mammalian target of rapamycin (mTOR) and/or p70S6 kinase (p70S6K) activity in cultured L6 myotubes in association with increased phosphorylation (P) of insulin receptor substrate 1 (IRS-1) at Ser636 and reduced insulin-stimulated glucose uptake; the mTOR inhibitor rapamycin blocks these effects of nicotine. GLUT-4, glucose transporter type 4, insulin-responsive; NACHR, nicotinic acetylcholine receptor; p85, PI3K regulatory subunit-α; p110, PI3K catalytic subunit polypeptide; PI3K, phosphoinositide 3-kinase. American Diabetes Association, Bajaj, M. et al. Nicotine and insulin resistance: when the smoke clears. Diabetes 61, 3078–3080 (2012). Copyright and all rights reserved. Material from this publication has been used with the permission of American Diabetes Association.