Role of the inflammasome in insulin resistance and type 2 diabetes mellitus

Abstract

The inflammasome is a protein complex composed of a variety of proteins in cells and which participates in the innate immune response of the body. It can be activated by upstream signal regulation and plays an important role in pyroptosis, apoptosis, inflammation, tumor regulation, etc. In recent years, the number of metabolic syndrome patients with insulin resistance (IR) has increased year by year, and the inflammasome is closely related to the occurrence and development of metabolic diseases. The inflammasome can directly or indirectly affect conduction of the insulin signaling pathway, involvement the occurrence of IR and type 2 diabetes mellitus (T2DM). Moreover, various therapeutic agents also work through the inflammasome to treat with diabetes. This review focuses on the role of inflammasome on IR and T2DM, pointing out the association and utility value. Briefly, we have discussed the main inflammasomes, including NLRP1, NLRP3, NLRC4, NLRP6 and AIM2, as well as their structure, activation and regulation in IR were described in detail. Finally, we discussed the current therapeutic options-associated with inflammasome for the treatment of T2DM. Specially, the NLRP3-related therapeutic agents and options are widely developed. In summary, this article reviews the role of and research progress on the inflammasome in IR and T2DM.

Influences of vitiligo‐associated characteristics on the occurrence of diabetes mellitus: Interactive analysis of a cross‐sectional study

“…The exposure to smoke has been discovered to stimulate the activation of inflammasomes and the accumulation of free radicals in both the circulatory system and local keratinocytes of the skin 38–41 . Both the activation of inflammasome as well as the accumulation of ROS have been firmly established as crucial factors in the development of vitiligo and diabetes 42,43 . In our study, we observed no distinct benefit for vitiligo development, which is more in line with our expectations.…”

“…[38][39][40][41] Both the activation of inflammasome as well as the accumulation of ROS have been firmly established as crucial factors in the development of vitiligo and diabetes. 42,43 In our study, we observed no distinct benefit for vitiligo development, which is more in line with our expectations. Considering the harm to DM occurrence caused by smoking, especially the additive effect of smoking and disease severity, we strongly recommend that patients with vitiligo should quit smoking.…”

Association of salivary levels of DNA sensing inflammasomes AIM2, IFI16, and cytokine IL18 with periodontitis and diabetes

“…36 Hyperglycemia also causes deregulation of NLRP1,3,6, NLRC4, and AIM2 and is associated with insulin resistance and development of diabetic complications. 37 There is considerable evidence that both of the diseases are epigenetically altered, resulting in the upregulation of inflammasome components. 38 This study analyzed the association of periodontitis and diabetes with salivary levels of AIM2, IFI16, and the potential confounders that could mediate the observed relationship.…”

“…The fundamental requirement for AIM2 inflammasome activation is the presence of cell free DNA (cfDNA). 37 These are small DNA fragments present in plasma, serum, urine, and other fluids in our body, inclusive of saliva. 43 cfDNA is derived from cell necrosis, apoptosis, and autonomic release following cellular synthesis of nucleic acids and represents nuclear as well as mitochondrial DNA (mtDNA).…”

“…There is an imbalance of inflammasomes NLRP3 and AIM2 and its negative regulators like pyrin only proteins (POPs), caspase recruitment domain only proteins (COPs), and tripartite motif family proteins (TRIMs) in gingiva of periodontitis patients 36 . Hyperglycemia also causes deregulation of NLRP1,3,6, NLRC4, and AIM2 and is associated with insulin resistance and development of diabetic complications 37 . There is considerable evidence that both of the diseases are epigenetically altered, resulting in the upregulation of inflammasome components 38 …”