2015-Molecular and cellular mechanisms linking inflammation to insulin resistance and β-cell dysfunction

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1、53541REVIEWARTICLE552563574Molecularandcellularmechanismslinking585596inflammationtoinsulinresistanceandb-cell6078Q1dysfunction6162963106411Q44HADIKHODABANDELOO,SATTARGORGANI-FIRUZJAEE,SHAHRIYARPANAHI,and6512REZAMESHKANI66136714TEHRAN,ISLAMICREPUBLICOFIRAN681569

2、1670177118Obesityisamajorpublichealthproblemworldwideandisassociatedwithanincreasedriskofdevelopingtype2diabetes.Itisnowcommonlyacceptedthat721920chronicinflammationassociatedwithobesityinducesinsulinresistanceandb-cell73dysfunctionindiabeticpatients.Obesity-ass

3、ociatedinflammationischaracterized7421byincreasedabundanceofmacrophagesandenhancedproductionofinflamma-7522torycytokinesinadiposetissue.Adiposetissuemacrophagesaresuggestedtobe7623themajorsourceoflocalandsystemicinflammatorymediatorssuchastumornecro-7724sisfactora

4、lpha,interleukin(IL)-1b,andIL-6.Thesecytokinesinduceinsulinresistance7825intheinsulintargettissuesbyactivatingthesuppressorsofcytokinesignaling7926proteins;severalkinasessuchasc-JunN-terminalkinase,IkBkinaseb,andprotein8027kinaseC;induciblenitricoxidesynthase;e

5、xtracellular-signal-regulatedkinase;8128andproteintyrosinephosphatasessuchasproteintyrosinephosphatase1B.These8229factorsinturnimpairtheinsulinsignalingattheinsulinreceptorandtheinsulinrecep-torsubstratelevels.Thesameprocessmostlikelyoccursinthepancreasasitcon-

6、8330tainsapooloftissue-residentmacrophages.Highconcentrationsofglucoseor8431palmitateviathechemokineproductionpromotefurtherimmunecellmigration8532andinfiltrationtotheislets.Theseeventsultimatelyinduceinflammatoryresponses8633leadingtotheapoptosisinthepancreaticb

7、cells.Inthisreview,thecellularand8734molecularplayersthatparticipateintheregulationofobesity-inducedinflammation8835arediscussed,withparticularattentionbeingplacedontherolesofthemolecular8936playerslinkinginflammationtoinsulinresistanceandb-celldysfunction.(Trans

8、la-9037tionalResearch2015;-:1–27)91389239Abbreviations:ACC¼acetyl–CoAcarboxylase;AMPK¼AMP-activatedproteinkinase;ASC¼9340apoptosis-associatedspeck-likeproteincontainingaCARD