Immunometabolism in type 2 diabetes mellitus: tissue-specific interactions

Abstract

The immune system is frequently described in the context of its protective function against infections and its role in the development of autoimmunity. For more than a decade, the interactions between the immune system and metabolic processes have been reported, in effect creating a new research field, termed immunometabolism. Accumulating evidence supports the hypo thesis that the development of metabolic diseases may be linked to inflammation, and reflects, in some cases, the activation of immune responses. As such, immunometabolism is defined by 1) inflammation as a driver of disease development and/or 2) metabolic processes stimulating cellular differentiation of the immune components. In this review, the main factors capable of altering the immuno-metabolic communication leading to the development and establishment of obesity and diabetes are comprehensively presented. Tissue-specific immune responses suggested to impair metabolic processes are described, with an emphasis on the adipose tissue, gut, muscle, liver, and pancreas.

Comparative Screening of the Liver Gene Expression Profiles from Type 1 and Type 2 Diabetes Rat Models

“…In the liver, there is an M1 polarization of Kupffer cells, increased macrophage infiltration, increased neutrophil activity (neutrophil elastase), increased proinflammatory cytokine production, activation of PPAR-γ, NF-κB, TLR4 and inflammasomes. A comprehensive understanding of immunometabolism in T2D could provide new avenues for its therapeutic intervention [56].…”

Assessment of patient-to-patient and intra-individual human abdominal skin immune cell variability

“…The impact of this variation on the usefulness of abdominoplasty skin explants for research will depend on the experimental purpose and design. For example, a large influx of immune cells might be expected to enter immune-mediated diseased and/or inflamed skin [ 19 , 20 ], in which case the 2- to 7-fold differences in immune cell numbers we detected in otherwise healthy skin may have less of an impact if being used for comparative controls. However, the levels of immune cell variation would certainly be impactful if, for example, the focus was on biology connected to a specific subset, such as HLA-DR + cells, which varied 19-fold between patients.…”

The Cardiac-Kidney-Liver (CKL) syndrome: the “real entity” of type 2 diabetes mellitus

“…Apart from acute coronary syndrome (ACS) incidence, T2DM patients also have an increased risk of ACS mortality [13,14]. Of note, in a previous meta-analysis (30 prospective cohort studies, n = 1,148,188 individuals), the pooled women-to-men relative risk ratio (RRR) was 1.52 (95% CI: 1.32-1.76; p < 0.001) for CHD, 1.23 (95% CI: 1.09-1.39; p = 0.001) for stroke, 1.49 (95% CI: 1.11-2.00; p = 0.009) for cardiac death and 1.51 (95% CI: 1.23-1.85; p < 0.001) for total mortality [15]. These findings suggest that T2DM women are at a greater risk for CV morbidity and mortality, as well as all-cause death compared with T2DM men.…”

“…Overall, T2DM has been regarded as a potential CHD equivalent based on common pathophysiology mechanisms (e.g., oxidative stress, inflammation, endothelial dysfunction, platelet activation), risk factors (e.g., obesity, dyslipidemia, hyperten-sion, aging) and outcomes (e.g., HF, arrythmias, CV death and non-cardiac vascular diseases) [29][30][31]. Epicardial and pericardial adipose tissue also play a role in the development of T2DM-related CHD, AF and HF [32].…”