Inflammation and Insulin Resistance

Overview

Journal FEBS Lett

Specialty Biochemistry

Date 2007 Dec 7

PMID 18053812

Citations 434

Authors

Carl de Luca

Jerrold M Olefsky

Affiliations

Soon will be listed here.

Abstract

Obesity-induced chronic inflammation is a key component in the pathogenesis of insulin resistance and the Metabolic syndrome. In this review, we focus on the interconnection between obesity, inflammation and insulin resistance. Pro-inflammatory cytokines can cause insulin resistance in adipose tissue, skeletal muscle and liver by inhibiting insulin signal transduction. The sources of cytokines in insulin resistant states are the insulin target tissue themselves, primarily fat and liver, but to a larger extent the activated tissue resident macrophages. While the initiating factors of this inflammatory response remain to be fully determined, chronic inflammation in these tissues could cause localized insulin resistance via autocrine/paracrine cytokine signaling and systemic insulin resistance via endocrine cytokine signaling all of which contribute to the abnormal metabolic state.

Citing Articles

Perinatal adverse outcomes in twin pregnancies with preeclampsia complicated by distinct gestational diabetes subtypes.

Tang W, Kang Z, Zhao Y, Cai Q, Deng B, Zhou Z Acta Diabetol. 2025; .

PMID: 40088317 DOI: 10.1007/s00592-025-02444-z.

Association between C-reactive protein-triglyceride glucose index and testosterone levels among adult men: analyses of NHANES 2015-2016 data.

Zhang B, Gu Y, Chen Y, Xia W, Shao N, Zhuang Q Sex Med. 2025; 13(1):qfaf012.

PMID: 40061443 PMC: 11890278. DOI: 10.1093/sexmed/qfaf012.

The Impact of Sodium-Glucose Co-Transporter-2 Inhibition on Insulin Resistance and Inflammation in Patients with Type 2 Diabetes: A Retrospective Study.

Iordan L, Lazar S, Timar R, Popescu S, Sorescu T, Albai O Medicina (Kaunas). 2025; 61(2).

PMID: 40005325 PMC: 11857714. DOI: 10.3390/medicina61020209.

Targeting Ferroptosis in Parkinson's: Repurposing Diabetes Drugs as a Promising Treatment.

Duta C, Muscurel C, Dogaru C, Stoian I Int J Mol Sci. 2025; 26(4).

PMID: 40003982 PMC: 11855881. DOI: 10.3390/ijms26041516.

Non-Melanoma Skin Cancer: Assessing the Systemic Burden of the Disease.

Karampinis E, Koumaki D, Sgouros D, Nechalioti P, Toli O, Pappa G Cancers (Basel). 2025; 17(4).

PMID: 40002296 PMC: 11853326. DOI: 10.3390/cancers17040703.

References

Cai D, Yuan M, Frantz D, Melendez P, Hansen L, Lee J . Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med. 2005; 11(2):183-90. PMC: 1440292. DOI: 10.1038/nm1166. View

Ruan H, Hacohen N, Golub T, Van Parijs L, Lodish H . Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory. Diabetes. 2002; 51(5):1319-36. DOI: 10.2337/diabetes.51.5.1319. View

Schottelius A, Mayo M, Sartor R, Baldwin Jr A . Interleukin-10 signaling blocks inhibitor of kappaB kinase activity and nuclear factor kappaB DNA binding. J Biol Chem. 1999; 274(45):31868-74. DOI: 10.1074/jbc.274.45.31868. View

Di Gregorio G, Yao-Borengasser A, Rasouli N, Varma V, Lu T, Miles L . Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone. Diabetes. 2005; 54(8):2305-13. DOI: 10.2337/diabetes.54.8.2305. View

Iwasaki A, Medzhitov R . Toll-like receptor control of the adaptive immune responses. Nat Immunol. 2004; 5(10):987-95. DOI: 10.1038/ni1112. View

Aguirre V, Werner E, Giraud J, Lee Y, Shoelson S, White M . Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action. J Biol Chem. 2001; 277(2):1531-7. DOI: 10.1074/jbc.M101521200. View

Diehl A . Nonalcoholic steatosis and steatohepatitis IV. Nonalcoholic fatty liver disease abnormalities in macrophage function and cytokines. Am J Physiol Gastrointest Liver Physiol. 2001; 282(1):G1-5. DOI: 10.1152/ajpgi.00384.2001. View

Hevener A, Olefsky J, Reichart D, Audrey Nguyen M, Bandyopadyhay G, Leung H . Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones. J Clin Invest. 2007; 117(6):1658-69. PMC: 1868788. DOI: 10.1172/JCI31561. View

Asadullah K, Sterry W, Volk H . Interleukin-10 therapy--review of a new approach. Pharmacol Rev. 2003; 55(2):241-69. DOI: 10.1124/pr.55.2.4. View

10.

de Luca C, Olefsky J . Stressed out about obesity and insulin resistance. Nat Med. 2006; 12(1):41-2. DOI: 10.1038/nm0106-41. View

11.

Hirosumi J, Tuncman G, Chang L, Gorgun C, Uysal K, Maeda K . A central role for JNK in obesity and insulin resistance. Nature. 2002; 420(6913):333-6. DOI: 10.1038/nature01137. View

12.

Yu C, Chen Y, Cline G, Zhang D, Zong H, Wang Y . Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem. 2002; 277(52):50230-6. DOI: 10.1074/jbc.M200958200. View

13.

Pickersgill L, Litherland G, Greenberg A, Walker M, Yeaman S . Key role for ceramides in mediating insulin resistance in human muscle cells. J Biol Chem. 2007; 282(17):12583-9. DOI: 10.1074/jbc.M611157200. View

14.

Sugita H, Fujimoto M, Yasukawa T, Shimizu N, Sugita M, Yasuhara S . Inducible nitric-oxide synthase and NO donor induce insulin receptor substrate-1 degradation in skeletal muscle cells. J Biol Chem. 2005; 280(14):14203-11. DOI: 10.1074/jbc.M411226200. View

15.

Ozcan U, Cao Q, Yilmaz E, Lee A, Iwakoshi N, Ozdelen E . Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004; 306(5695):457-61. DOI: 10.1126/science.1103160. View

16.

Hotamisligil G, Peraldi P, Budavari A, Ellis R, White M, Spiegelman B . IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science. 1996; 271(5249):665-8. DOI: 10.1126/science.271.5249.665. View

17.

Lee J, Hwang D . The modulation of inflammatory gene expression by lipids: mediation through Toll-like receptors. Mol Cells. 2006; 21(2):174-85. View

18.

Kim J, Kim Y, Fillmore J, Chen Y, Moore I, Lee J . Prevention of fat-induced insulin resistance by salicylate. J Clin Invest. 2001; 108(3):437-46. PMC: 209353. DOI: 10.1172/JCI11559. View

19.

Sam Lee J, Pinnamaneni S, Eo S, Cho I, Pyo J, Kim C . Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites. J Appl Physiol (1985). 2005; 100(5):1467-74. DOI: 10.1152/japplphysiol.01438.2005. View

20.

Straczkowski M, Dzienis-Straczkowska S, Stepien A, Kowalska I, Szelachowska M, Kinalska I . Plasma interleukin-8 concentrations are increased in obese subjects and related to fat mass and tumor necrosis factor-alpha system. J Clin Endocrinol Metab. 2002; 87(10):4602-6. DOI: 10.1210/jc.2002-020135. View