Cardiovasc Prev Pharmacother.  2021 Apr;3(2):31-37. 10.36011/cpp.2021.3.e5.

Inflammation in Metabolic Diseases and Insulin Resistance

• Lee WY

• KMID: 2536944
• DOI: http://doi.org/10.36011/cpp.2021.3.e5

Abstract

Increased inflammation and insulin resistance are commonly observed in obesity and diabetes. Inflammatory mediators secreted by the adipose tissue contribute to the pathogenesis of diabetes and cardiovascular diseases. Free fatty acids and pro-inflammatory cytokines from adipose tissue inhibit the intracellular insulin signaling pathway, further contributing to the progression of diabetes. Meta-analysis studies show that high sensitivity C-reactive protein can be used as a predictor of future all-cause mortality, including cardiovascular and cancer mortality. In addition to the discovery of novel therapeutic methods targeting inflammatory mediators, basic lifestyle interventions, such as regular exercise, healthy eating, and proper weight control, are absolutely crucial for reducing inflammation and preventing mortality.

Keyword

Diabetes mellitus; Inflammation; Insulin resistance; Metabolic diseases; Metabolic syndrome

Figure

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  Figure 1. Pio improves PA-induced β-cell impairment by suppressing the inflammatory response and ER stress. (A) MIN6 cells were incubated with 0.5 mM PA in the presence or absence of 10 µM Pio for 24 hours, and the glucose-stimulated (1 or 4.5 g/L) insulin secretion of MIN6 cells was evaluated. Secreted insulin was measured using a mouse insulin enzyme-linked immunosorbent assay kit. The values are representative of 6 independent experiments. (B) The expression of c-casp3, an apoptotic protein, was measured by Western blot analysis. (C) PARP activity is presented as the percentage of absorbance relative to the veh group. (D) Expression of TNFα, IL-6, and IL-1β was measured by real time reverse-transcription polymerase chain reaction, and normalized to ACTB. (E) ER stress proteins, including p-eIF2α, GRP78, c-ATF6, and CHOP, were measured by Western blot analysis. (F) Quantification of p-eIF2α, GRP78, and CHOP protein levels; the results were normalized to β-actin. Each value represents the mean of 3 experiments. ACTB = β-actin; c-ATF6 = cleaved-activating transcription factor 6; c-casp3 = cleaved caspase-3; CHOP = C/EBP homologous protein; ER = endoplasmic reticulum; GRP78 = glucose-regulated protein 78; IL = interleukin; MIN6 = mouse insulinoma 6; mRNA = messenger RNA; PA = palmitate; PARP = poly (adenosine diphosphate [ADP]-ribose) polymerase; p-eIF2α = phospho-eukaryotic translation initiation factor 2α; Pio = pioglitazone; t-casp3 = total caspase-3; TNFα = tumor necrosis factor alpha; Veh = vehicle. *p<0.01, †p<0.001 compared to the vehicle group; ‡p<0.05, §p<0.001 compared to the PA group (adapted from Hong SW, et al.24)).

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