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The Immune System and Inflammation in Type 2 Diabetes

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Abstract

The aim of this chapter is to show how immune cells participate during type 2 diabetes (T2D) establishment. Obesity is a major T2D driver, and it is also associated with insulin resistance (IR). These pathologies appear along with chronic inflammation characterized by an increased expression of proinflammatory molecules such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1β, resistin, and leptin, whereas anti-inflammatory cytokines as adiponectin, IL-4, IL-10, and IL-1Ra are decreased. The inflammatory response is triggered, and it occurs predominantly in adipose tissue (AT).

Immune cells that secrete many inflammatory effectors related to T2D are macrophages, lymphocytes T and B-2, natural killer (NK), Th1, Th2, Th17, T regulatory, invariant (i)NKT, eosinophils, dendritic (DC), and mast cells. In obesity conditions, macrophage AT population shifts from M2 to the M1 type, the first express anti-inflammatory and the last express proinflammatory cytokines; moreover, a decreased frequency of DC has been observed on AT. Mast cells in presence of high glucose levels express proinflammatory cytokines. Proinflammatory γδ T, Th1, and CD8+ T cells increased in response to a high-fat diet (HFD) in mice, and they are concomitant with a low abundance of anti-inflammatory NK, Th2, and Treg cells, especially in visceral AT (VAT). The same effect was observed on subjects with morbid obesity as they also exhibit a selective increase of Th CD4+ cells.

Finally, it is showing some strategies designed to inhibit or decrease the deleterious inflammatory effects caused by adipocytes and immune cells in human T2D.

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Authors and Affiliations

  1. Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional, Siglo XXI, Mexico City, Mexico

    Rebeca García Macedo

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  1. Multidisciplinary Diabetes Center, Mexico City, Mexico

    Joel Rodriguez-Saldana

Glossary

Adipokine

A cytokine or hormone that is secreted by adipose tissue.

Chemokines

Are signaling proteins secreted by cells, whose main function is to act as a chemoattractant to guide the migration of near cells. They are implicated in various diseases, such as cancer, autoimmune disorders, and diabetes.

Cytokine

Small proteins secreted and released by cells, they have a specific effect on the interactions and communications between cells.

Diet-induced obesity (DIO)

Obesity mouse model induced by high-fat diet.

FA

A carboxylic acid with aliphatic chains of 4–28 carbons, which can be esterified with glycerol to form triacylglycerols, the main stored form of lipids.

IgG, IgM

Are members of immunoglobulin (Ig) superfamily; they are ubiquitously present in several cells and tissues of vertebrates and share structural homology with cell adhesion molecules and some cytokines.

Innate immune cells

Are white blood cells that mediate innate immunity and include basophils, dendritic cells, eosinophils, mast cells, monocytes, macrophages, neutrophils, and natural killer cells.

Mitogen-activated protein kinase

(MAPK) a mammalian Ser/Thr protein kinase.

NF-κB

(Nuclear factor-κB) is a ubiquitous transcription factor involved in the control of processes, such as immune and inflammatory responses, developmental, cellular growth, and apoptosis. The NF-κB pathway has been considered as proinflammatory signaling pathway, based on the role of NF-κB in the expression of proinflammatory genes including cytokines, chemokines, and adhesion molecules.

Omental adipose tissue

The fat depot found within the peritoneum, in close association with the stomach and other internal organs.

PPARγ

(Peroxisome proliferator-activated receptor gamma) is an essential transcription regulator of the adipocyte differentiation and is required for mature adipocyte function.

Salicylates

A group of derivatives of salicylic acid, including aspirin and acetylsalicylic acid, which are widely used as analgesics, and anti-inflammatory medicaments

Thiazolidinediones

Antidiabetic drugs used therapeutically, which are known to be high-affinity ligand activators of PPARγ.

White adipose tissue (WAT)

The predominant fat storage tissue in animals, consisting mostly of adipocytes but also other cell types as mast cells and macrophages.

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Macedo, R.G. (2019). The Immune System and Inflammation in Type 2 Diabetes. In: Rodriguez-Saldana, J. (eds) The Diabetes Textbook. Springer, Cham. https://doi.org/10.1007/978-3-030-11815-0_11

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