PMID- 22966072
OWN - NLM
STAT- MEDLINE
DCOM- 20130125
LR  - 20211203
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 61
IP  - 12
DP  - 2012 Dec
TI  - Novel and reversible mechanisms of smoking-induced insulin resistance in humans.
PG  - 3156-66
LID - 10.2337/db12-0418 [doi]
AB  - 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.
FAU - Bergman, Bryan C
AU  - Bergman BC
AD  - Department of Endocrinology, Diabetes, and Metabolism, University of Colorado 
      Denver, Denver, Colorado, USA. bryan.bergman@ucdenver.edu
FAU - Perreault, Leigh
AU  - Perreault L
FAU - Hunerdosse, Devon
AU  - Hunerdosse D
FAU - Kerege, Anna
AU  - Kerege A
FAU - Playdon, Mary
AU  - Playdon M
FAU - Samek, Ali M
AU  - Samek AM
FAU - Eckel, Robert H
AU  - Eckel RH
LA  - eng
GR  - R01 DK089170/DK/NIDDK NIH HHS/United States
GR  - F32 DK059739/DK/NIDDK NIH HHS/United States
GR  - DK-059739/DK/NIDDK NIH HHS/United States
GR  - DK-064811/DK/NIDDK NIH HHS/United States
GR  - DK-26356/DK/NIDDK NIH HHS/United States
GR  - R01 DK026356/DK/NIDDK NIH HHS/United States
GR  - RR-00036/RR/NCRR NIH HHS/United States
GR  - K23 DK064811/DK/NIDDK NIH HHS/United States
GR  - M01 RR000036/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120910
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (IRS1 protein, human)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 6M3C89ZY6R (Nicotine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
CIN - Diabetes. 2012 Dec;61(12):3078-80. PMID: 23172960
MH  - Adult
MH  - Blotting, Western
MH  - Female
MH  - Humans
MH  - Insulin Receptor Substrate Proteins/genetics/metabolism
MH  - Insulin Resistance/genetics/*physiology
MH  - Male
MH  - Muscle, Skeletal/drug effects/metabolism
MH  - Nicotine/pharmacology
MH  - Phosphorylation/drug effects
MH  - Smoking/*adverse effects
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - Young Adult
PMC - PMC3501865
EDAT- 2012/09/12 06:00
MHDA- 2013/01/26 06:00
PMCR- 2013/12/01
CRDT- 2012/09/12 06:00
PHST- 2012/09/12 06:00 [entrez]
PHST- 2012/09/12 06:00 [pubmed]
PHST- 2013/01/26 06:00 [medline]
PHST- 2013/12/01 00:00 [pmc-release]
AID - db12-0418 [pii]
AID - 0418 [pii]
AID - 10.2337/db12-0418 [doi]
PST - ppublish
SO  - Diabetes. 2012 Dec;61(12):3156-66. doi: 10.2337/db12-0418. Epub 2012 Sep 10.