NLRP3 Inflammasome and Diabetes_Journal of Biomedical Engineering

Authors：

LIUQilin ,  LIJianwei

Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

LIJianwei, Email: jerryli678@yahoo.com

Keywords：

NLRP3 inflammasome; interleukin-1β; diabetes mellitus; targeted therapy

DOI：

10.7507/1001-5515.20140268

Video：

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Abstract Full text Figures/Tables Video References Cited by

Diabetes has become a global epidemic disease now. Its chronic progressive deterioration and the acute and chronic complications affect the quality of the patients' lives seriously. The prevention and treatment of diabetes has become one of the research focuses in recent years. NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome can recognize the metabolic stress signals, and cause caspase-1 activation and interleukin-1β (IL-1β) production, and is closely related to diabetes development. The latest studies have shown that NLRP3 inflammasome will be a new potential target for the treatment of diabetes. This article reviews the activation and regulation of NLRP3 inflammasome, and the effect of NLRP3 inflammasome on glucose metabolism and its targeted therapy in diabetes.

Citation： LIUQilin, LIJianwei. NLRP3 Inflammasome and Diabetes. Journal of Biomedical Engineering, 2014, 31(6): 1414-1418. doi: 10.7507/1001-5515.20140268 Copy

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2.	SCHRODER K, TSCHOPP J. The inflammasomes[J]. Cell, 2010, 140(6):821-832.
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13.	STIENSTRA R, TACK C J, KANNEGANTI T D, et al. The inflammasome puts obesity in the danger zone[J]. Cell Metab, 2012, 15(1):10-18.
14.	VANDANMAGSAR B, YOUM Y H, RAVUSSIN A, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance[J]. Nat Med, 2011, 17(2):179-188.
15.	ZHOU R, TARDIVEL A, THORENS B, et al. Thioredoxin-interacting protein links oxidative stress to inflammasome activation[J]. Nat Immunol, 2010, 11(2):136-140.
16.	KOENEN T B, STIENSTRA R, VAN TITS L J, et al. Hyperglycemia activates caspase-1 and TXNIP-mediated IL-1beta transcription in human adipose tissue[J]. Diabetes, 2011, 60(2):517-524.
17.	MASTERS S L, DUNNE A, SUBRAMANIAN S L, et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes[J]. Nat Immunol, 2010, 11(10):897-904.
18.	ABDERRAHMANI A, NIEDERHAUSER G, FAVRE D, et al. Human high-density lipoprotein particles prevent activation of the JNK pathway induced by human oxidised low-density lipoprotein particles in pancreatic beta cells[J]. Diabetologia, 2007, 50(6):1304-1314.
19.	LARSEN C M, FAULENBACH M, VAAG A, et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus[J]. N Engl J Med, 2007, 356(15):1517-1526.
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21.	SUMPTER K M, ADHIKARI S, GRISHMAN E K, et al. Preliminary studies related to anti-interleukin-1β therapy in children with newly diagnosed type 1 diabetes[J]. Pediatr Diabetes, 2011, 12(7):656-667.
22.	RISSANEN A, HOWARD C P, BOTHA J, et al. Effect of anti-IL-1β antibody (canakinumab) on insulin secretion rates in impaired glucose tolerance or type 2 diabetes:results of a randomized, placebo-controlled trial[J]. Diabetes Obes Metab, 2012, 14(12):1088-1096.
23.	OWYANG A M, MAEDLER K, GROSS L, et al. XOMA 052, an anti-IL-1betamonoclonal antibody, improves glucose control andbeta-cell function in the diet-induced obesity mouse model[J]. Endocrinology, 2010, 151(6):2515-2527.
24.	STIENSTRA R, JOOSTEN L A, KOENEN T, et al. The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity[J]. Cell Metab, 2010, 12(6):593-605.
25.	MITROULIS I, SKENDROS P, RITIS K. Targeting IL-1beta in disease:the expanding role of NLRP3 inflammasome[J]. Eur J Intern Med, 2010, 21(3):157-163.

1. YANG W, LU J, WENG J, et al. Prevalence of diabetes among men and women in China[J]. N Engl J Med, 2010, 362(12):1090-1101.
2. SCHRODER K, TSCHOPP J. The inflammasomes[J]. Cell, 2010, 140(6):821-832.
3. LAMKANFI M, WALLE L V, KANNEGANTI T D. Deregulated inflammasome signaling in disease[J]. Immunol Rev, 2011, 243(1):163-173.
4. DE NARDO D, LATZ E. NLRP3 inflammasomes link inflammation and metabolic disease[J]. Trends Immunol, 2011, 32(8):373-379.
5. BRYANT C, FITZGERALD K A. Molecular mechanisms involved in inflammasome activation[J]. Trends Cell Biol, 2009, 19(9):455-464.
6. ZHOU R, YAZDI A S, MENU P, et al. A role for mitochondria in NLRP3 inflammasome activation[J]. Nature, 2011, 469(7329):221-225.
7. MARTINON F. Signaling by ROS drives inflammasome activation[J]. Eur J Immunol, 2010, 40(3):616-619.
8. SCHRODER K, ZHOU R, TSCHOPP J. The NLRP3 inflammasome:a sensor for metabolic danger?[J]. Science, 2010, 327(5963):296-300.
9. MAEDLER K, DHARMADHIKARI G, SCHUMANN D M, et al. Interleukin-targeted therapy for metabolic syndrome and type 2 diabetes[J]. Handb Exp Pharmacol, 2011, (203):257-278.
10. KOENEN T B, STIENSTRA R, VAN TITS L J, et al. The inflammasome and caspase-1 activation:a new mechanism underlying increased inflammatory activity in human visceral adipose tissue[J]. Endocrinology, 2011, 152(10):3769-3778.
11. MASON D R, BECK P L, MURUVE D A. Nucleotide-binding oligomerization domain-like receptors and inflammasomes in the pathogenesis of non-microbial inflammation and diseases[J]. J Innate Immun, 2012, 4(1):16-30.
12. CANI P D, BIBILONI R, KNAUF C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice[J]. Diabetes, 2008, 57(6):1470-1481.
13. STIENSTRA R, TACK C J, KANNEGANTI T D, et al. The inflammasome puts obesity in the danger zone[J]. Cell Metab, 2012, 15(1):10-18.
14. VANDANMAGSAR B, YOUM Y H, RAVUSSIN A, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance[J]. Nat Med, 2011, 17(2):179-188.
15. ZHOU R, TARDIVEL A, THORENS B, et al. Thioredoxin-interacting protein links oxidative stress to inflammasome activation[J]. Nat Immunol, 2010, 11(2):136-140.
16. KOENEN T B, STIENSTRA R, VAN TITS L J, et al. Hyperglycemia activates caspase-1 and TXNIP-mediated IL-1beta transcription in human adipose tissue[J]. Diabetes, 2011, 60(2):517-524.
17. MASTERS S L, DUNNE A, SUBRAMANIAN S L, et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes[J]. Nat Immunol, 2010, 11(10):897-904.
18. ABDERRAHMANI A, NIEDERHAUSER G, FAVRE D, et al. Human high-density lipoprotein particles prevent activation of the JNK pathway induced by human oxidised low-density lipoprotein particles in pancreatic beta cells[J]. Diabetologia, 2007, 50(6):1304-1314.
19. LARSEN C M, FAULENBACH M, VAAG A, et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus[J]. N Engl J Med, 2007, 356(15):1517-1526.
20. LARSEN C M, FAULENBACH M, VAAG A, et al. Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes[J]. Diabetes Care, 2009, 32(9):1663-1668.
21. SUMPTER K M, ADHIKARI S, GRISHMAN E K, et al. Preliminary studies related to anti-interleukin-1β therapy in children with newly diagnosed type 1 diabetes[J]. Pediatr Diabetes, 2011, 12(7):656-667.
22. RISSANEN A, HOWARD C P, BOTHA J, et al. Effect of anti-IL-1β antibody (canakinumab) on insulin secretion rates in impaired glucose tolerance or type 2 diabetes:results of a randomized, placebo-controlled trial[J]. Diabetes Obes Metab, 2012, 14(12):1088-1096.
23. OWYANG A M, MAEDLER K, GROSS L, et al. XOMA 052, an anti-IL-1betamonoclonal antibody, improves glucose control andbeta-cell function in the diet-induced obesity mouse model[J]. Endocrinology, 2010, 151(6):2515-2527.
24. STIENSTRA R, JOOSTEN L A, KOENEN T, et al. The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity[J]. Cell Metab, 2010, 12(6):593-605.
25. MITROULIS I, SKENDROS P, RITIS K. Targeting IL-1beta in disease:the expanding role of NLRP3 inflammasome[J]. Eur J Intern Med, 2010, 21(3):157-163.

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NLRP3 Inflammasome and Diabetes

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