Innate Immunity, Insulin Resistance and Type 2 Diabetes

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2011 Nov 30

PMID 22124608

Citations 39

Authors

J M Fernandez-Real

J C Pickup

Affiliations

Soon will be listed here.

Abstract

In this edition of 'Then and now' the initial studies by J.C. Pickup and colleagues supporting the hypothesis that type 2 diabetes is caused by activated innate immunity, published in Diabetologia in 1997 (40:1286-1292), are discussed. These initial findings led to research that has uncovered links between insulin resistance, obesity, circulating immune markers, immunogenetic susceptibility, macrophage function and chronic infection. Genetic variations leading to the altered production or function of circulating innate immune proteins, cellular pattern recognition receptors and inflammatory cytokines are linked to obesity, insulin resistance and type 2 diabetes. Components of the innate immune system in the muscle, bone, liver and adipose tissue, as well as macrophages, have been revealed to play a role in systemic insulin action. Evolutionary pressures, such as acute infections at the population level (pandemics) and chronic low exposure to environmental products or infectious agents, may have contributed to increased susceptibility and to the current increase in the prevalence of insulin resistance and type 2 diabetes.

Citing Articles

Association of Periodontal Condition With Impaired Glucose Tolerance: Results of a 15-Year Follow-Up Study.

Myllymaki V, Ylostalo P, Suominen A, Knuuttila M, Rajala U, Keinanen-Kiukaanniemi S Clin Exp Dent Res. 2024; 10(6):e70023.

PMID: 39400977 PMC: 11734188. DOI: 10.1002/cre2.70023.

Regulatory T cells and bioenergetics of peripheral blood mononuclear cells linked to pediatric obesity.

Rose S, Landes R, Vyas K, Delhey L, Blossom S Immunometabolism (Cobham). 2024; 6(2):e00040.

PMID: 38680993 PMC: 11045398. DOI: 10.1097/IN9.0000000000000040.

Comparison of hs-CRP in Adult Obesity and Central Obesity in Indonesia Based on Omega-3 Fatty Acids Intake: Indonesian Family Life Survey 5 (IFLS 5) Study.

Megawati G, Indraswari N, Johansyah A, Kezia C, Herawati D, Gurnida D Int J Environ Res Public Health. 2023; 20(18).

PMID: 37754594 PMC: 10530835. DOI: 10.3390/ijerph20186734.

The effects of acarbose treatment on cardiovascular risk factors in impaired glucose tolerance and diabetic patients: a systematic review and dose-response meta-analysis of randomized clinical trials.

Zamani M, Nikbaf-Shandiz M, Aali Y, Rasaei N, Zarei M, Shiraseb F Front Nutr. 2023; 10:1084084.

PMID: 37599681 PMC: 10433190. DOI: 10.3389/fnut.2023.1084084.

Serum γ-glutamyltransferase level and incidence risk of metabolic syndrome in community dwelling adults: longitudinal findings over 12 years.

Kwak J, Seo I, Lee Y Diabetol Metab Syndr. 2023; 15(1):29.

PMID: 36823659 PMC: 9948354. DOI: 10.1186/s13098-023-01000-5.

References

Turnbaugh P, Ley R, Mahowald M, Magrini V, Mardis E, Gordon J . An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006; 444(7122):1027-31. DOI: 10.1038/nature05414. View

Moreno-Navarrete J, Ortega F, Sabater M, Ricart W, Fernandez-Real J . Telomere length of subcutaneous adipose tissue cells is shorter in obese and formerly obese subjects. Int J Obes (Lond). 2010; 34(8):1345-8. DOI: 10.1038/ijo.2010.49. View

Stumvoll M, Tataranni P, Stefan N, Vozarova B, Bogardus C . Glucose allostasis. Diabetes. 2003; 52(4):903-9. DOI: 10.2337/diabetes.52.4.903. View

Krishnapuram R, Dhurandhar E, Dubuisson O, Kirk-Ballard H, Bajpeyi S, Butte N . Template to improve glycemic control without reducing adiposity or dietary fat. Am J Physiol Endocrinol Metab. 2011; 300(5):E779-89. PMC: 3093976. DOI: 10.1152/ajpendo.00703.2010. View

Olefsky J, Glass C . Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010; 72:219-46. DOI: 10.1146/annurev-physiol-021909-135846. View

Pickup J, Mattock M, Chusney G, Burt D . NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia. 1997; 40(11):1286-92. DOI: 10.1007/s001250050822. View

Fernandez-Real J, Pickup J . Innate immunity, insulin resistance and type 2 diabetes. Trends Endocrinol Metab. 2007; 19(1):10-6. DOI: 10.1016/j.tem.2007.10.004. View

Minamino T, Orimo M, Shimizu I, Kunieda T, Yokoyama M, Ito T . A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat Med. 2009; 15(9):1082-7. DOI: 10.1038/nm.2014. View

Reyes A, Haynes M, Hanson N, Angly F, Heath A, Rohwer F . Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature. 2010; 466(7304):334-8. PMC: 2919852. DOI: 10.1038/nature09199. View

10.

Bonnefond A, Froguel P, Vaxillaire M . The emerging genetics of type 2 diabetes. Trends Mol Med. 2010; 16(9):407-16. DOI: 10.1016/j.molmed.2010.06.004. View

11.

Emilsson V, Thorleifsson G, Zhang B, Leonardson A, Zink F, Zhu J . Genetics of gene expression and its effect on disease. Nature. 2008; 452(7186):423-8. DOI: 10.1038/nature06758. View

12.

Ortega F, Moreno-Navarrete J, Pardo G, Sabater M, Hummel M, Ferrer A . MiRNA expression profile of human subcutaneous adipose and during adipocyte differentiation. PLoS One. 2010; 5(2):e9022. PMC: 2814866. DOI: 10.1371/journal.pone.0009022. View

13.

Amar J, Chabo C, Waget A, Klopp P, Vachoux C, Bermudez-Humaran L . Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment. EMBO Mol Med. 2011; 3(9):559-72. PMC: 3265717. DOI: 10.1002/emmm.201100159. View

14.

Fernandez-Real J, Ricart W . Insulin resistance and inflammation in an evolutionary perspective: the contribution of cytokine genotype/phenotype to thriftiness. Diabetologia. 1999; 42(11):1367-74. DOI: 10.1007/s001250051451. View

15.

Fernandez-Real J, Perez Del Pulgar S, Luche E, Moreno-Navarrete J, Waget A, Serino M . CD14 modulates inflammation-driven insulin resistance. Diabetes. 2011; 60(8):2179-86. PMC: 3142089. DOI: 10.2337/db10-1210. View

16.

Pickup J . Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care. 2004; 27(3):813-23. DOI: 10.2337/diacare.27.3.813. View

17.

Huth C, Heid I, Vollmert C, Gieger C, Grallert H, Wolford J . IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies. Diabetes. 2006; 55(10):2915-21. DOI: 10.2337/db06-0600. View