Mechanisms for Insulin Resistance: Common Threads and Missing Links

被引：1632

作者：

Samuel, Varman T. ^{[1
,4
]}

Shulman, Gerald I. ^{[1
,2
,3
]}

机构：

[1] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA

[2] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA

[3] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA

[4] Vet Affairs Med Ctr, West Haven, CT 06516 USA

来源：

CELL | 2012年 / 148卷 / 05期

关键词：

PROTEIN-KINASE-C; FATTY LIVER-DISEASE; ADIPOSE TRIGLYCERIDE LIPASE; TUMOR-NECROSIS-FACTOR; ENDOPLASMIC-RETICULUM STRESS; DIET-INDUCED OBESITY; NF-KAPPA-B; DEPENDENT DIABETES-MELLITUS; INDUCED HEPATIC STEATOSIS; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY;

D O I：

10.1016/j.cell.2012.02.017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Insulin resistance is a complex metabolic disorder that defies explanation by a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway, and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, these cellular changes may converge to promote the accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, a common final pathway leading to impaired insulin signaling and insulin resistance.

引用

页码：852 / 871

页数：20

共 178 条

[11] Influence of the Hepatic Eukaryotic Initiation Factor 2α (eIF2α) Endoplasmic Reticulum (ER) Stress Response Pathway on Insulin-mediated ER Stress and Hepatic and Peripheral Glucose Metabolism [J].

Birkenfeld, Andreas L. ;

Lee, Hui-Young ;

Majumdar, Sachin ;

Jurczak, Michael J. ;

Camporez, Joao Paulo ;

Jornayvaz, Francois R. ;

Frederick, David W. ;

Guigni, Blas ;

Kahn, Mario ;

Zhang, Dongyang ;

Weismann, Dirk ;

Arafat, Ayman M. ;

Pfeiffer, Andreas F. ;

Lieske, Stefanie ;

Oyadomari, Seiichi ;

Ron, David ;

Samuel, Varman T. ;

Shulman, Gerald I. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (42) :36163-36170

[12] Plasma Membrane Subdomain Compartmentalization Contributes to Distinct Mechanisms of Ceramide Action on Insulin Signaling [J].

Blouin, Cedric M. ;

Prado, Cecilia ;

Takane, Karen K. ;

Lasnier, Francoise ;

Garcia-Ocana, Adolfo ;

Ferre, Pascal ;

Dugail, Isabelle ;

Hajduch, Eric .

DIABETES, 2010, 59 (03) :600-610

[13] Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-κB pathway in rat liver [J].

Boden, G ;

She, PX ;

Mozzoli, M ;

Cheung, P ;

Gumireddy, K ;

Reddy, P ;

Xiang, XQ ;

Luo, ZJ ;

Ruderman, N .

DIABETES, 2005, 54 (12) :3458-3465

[14] Pigment Epithelium-Derived Factor Regulates Lipid Metabolism via Adipose Triglyceride Lipase [J].

Borg, Melissa L. ;

Andrews, Zane B. ;

Duh, Ella J. ;

Zechner, Rudolf ;

Meikle, Peter J. ;

Watt, Matthew J. .

DIABETES, 2011, 60 (05) :1458-1466

[15] Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence [J].

Boyle, James P. ;

Thompson, Theodore J. ;

Gregg, Edward W. ;

Barker, Lawrence E. ;

Williamson, David F. .

POPULATION HEALTH METRICS, 2010, 8

[16] CGI-58 knockdown in mice causes hepatic steatosis but prevents diet-induced obesity and glucose intolerance [J].

Brown, J. Mark ;

Betters, Jenna L. ;

Lord, Caleb ;

Ma, Yinyan ;

Han, Xianlin ;

Yang, Kui ;

Alger, Heather M. ;

Melchior, John ;

Sawyer, Janet ;

Shah, Ramesh ;

Wilson, Martha D. ;

Liu, Xiuli ;

Graham, Mark J. ;

Lee, Richard ;

Crooke, Rosanne ;

Shulman, Gerald I. ;

Xue, Bingzhong ;

Shi, Hang ;

Yu, Liqing .

JOURNAL OF LIPID RESEARCH, 2010, 51 (11) :3306-3315

[17] Cytokine regulation of skeletal muscle fatty acid metabolism:: effect of interleukin-6 and tumor necrosis factor-α [J].

Bruce, CR ;

Dyck, DJ .

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2004, 287 (04) :E616-E621

[18] Interleukin 1 and tumor necrosis factor in obese alcoholics compared with normal-weight patients [J].

Bunout, D ;

Munoz, C ;

Lopez, M ;

delaMaza, MP ;

Schlesinger, L ;

Hirsch, S ;

Pettermann, M .

AMERICAN JOURNAL OF CLINICAL NUTRITION, 1996, 63 (03) :373-376

[19] IKKβ/NF-κB activation causes severe muscle wasting in mice [J].

Cai, DS ;

Frantz, JD ;

Tawa, NE ;

Melendez, PA ;

Oh, BC ;

Lidov, HGW ;

Hasselgren, PO ;

Frontera, WR ;

Lee, J ;

Glass, DJ ;

Shoelson, SE .

CELL, 2004, 119 (02) :285-298

[20] Regulation of adiponutrin expression by feeding conditions in rats is altered in the obese state [J].

Caimari, Antoni ;

Oliver, Paula ;

Palou, Andreu .

OBESITY, 2007, 15 (03) :591-599

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