Interleukin-37 sensitize the elderly type 2 diabetic patients to insulin therapy through suppressing the gut microbiota dysbiosis

Mol Immunol. 2019 Aug:112:322-329. doi: 10.1016/j.molimm.2019.06.008. Epub 2019 Jun 22.

Abstract

Objective: The morbidity and prevalence of type 2 diabetes mellitus (DM) are increasing in the elderly population. Interleukin 37 (IL-37) play important roles in anti-inflammatory and anti-bacteria immune responses, but its role in the development of type 2 DM in the elderly is unclear. Therefore, we investigated whether IL-37 is associated with type 2 DM in the elderly and the underlying mechanism.

Methods: Hospitalized patients (aged 65-95 years) with recently diagnosed type 2 diabetes mellitus were studied retrospectively and compared with healthy subjects without glucose metabolism abnormalities. A diabetic mouse model was established by feeding ob/ob mice (C57BL/6) a high-fat, carbohydrate-free diet. Plasma glucose and insulin levels were determined by glucose oxidase assay and radioimmunoassay, respectively. The IL-37 expression level was determined by real-time PCR, western blot and ELISA (Enzyme-linked immunoassay).

Results: Statistic analysis showed that the IL-37 level was significantly associated with type 2 DM and insulin resistance in the elderly. The patients were then divided into insulin therapy sensitive and resistant group according to their response to insulin therapy. Data showed that the IL-37 was highly expressed in the insulin therapy sensitive group. And this was related to the less severe gut microbiota dysbiosis. In the mice model, overexpressing the IL-37 could suppress the gut microbiota dysbiosis and also the diabetes development.

Conclusion: Thus our results showed that higher IL-37 was associated with increased insulin sensitive in elderly type 2 DM patients through suppressing the gut microbiota dysbiosis.

Keywords: Elderly; Gut microbiota dysbiosis; Insulin; Interleukin-37; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Cell Line
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / microbiology
  • Diabetes Mellitus, Type 2 / immunology*
  • Diabetes Mellitus, Type 2 / microbiology
  • Diet, High-Fat / adverse effects
  • Dysbiosis / immunology*
  • Dysbiosis / microbiology
  • Female
  • Gastrointestinal Microbiome / immunology*
  • HEK293 Cells
  • Humans
  • Insulin Resistance / immunology
  • Interleukin-1 / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL

Substances

  • IL37 protein, human
  • Interleukin-1