Table 1.

Some key inflammatory pathways of diabetes proven in mice.

Pathway	Model	Findings
NOD-, LRR- and pyrin-domain-containing protein 3 (NLRP3) inflammasome activation: protein complex triggering inflammatory mediator production	Streptozotocin-induced diabetic mice	Microglia NLRP3 proteins were highly expressed, and serum cytokines IL-1β, IL6, IL18, and TNFα were increased in streptozotocin-induced diabetic mice [34]
Endothelial NF-κB signaling: complex of transcription factors that regulate cytokine gene expression and the inflammatory response	Diabetic C57BL/KsJ db/db mice compared to healthy mice	The mRNA and protein levels of NF-κB and TLR4 were significantly higher in the db/db mice compared to normal control group [35]
	E-DNIκB mice (transgenic mice expressing dominant-negative IκB under the Tie2 promoter/enhancer)	Endothelial NF-κB inhibition ameliorates insulin resistance and improves glucose homeostasis via reduced aortic expression of adhesion molecules, upregulation of eNOS signaling, reduced macrophage infiltration, and iNOS expression in adipose tissue [36]
Major inflammatory cytokines secretion: IL-1β, IL-6, IL-18, and TNF-α	Diabetic C57BL/KsJ db/db mice compared to healthy mice	The serum levels of IL-1β, IL-6, IL-18, and TNF-α in the db/db mice were significantly higher compared to healthy control group [35]
	Male db/db mice	IL-1β, IL-18, and TNF-α levels were increased in liver of db/db mice compared to healthy mice [37]
JNK pathway activation: one of the major signaling cassettes of the mitogen-activated protein kinase (MAPK) signaling pathway	Apolipoprotein E/low-density lipoprotein receptor double-knockout (AL) mice	Hepatic inflammation and dyslipidemia were increased in AL mice on 35-week Western diet (WD) compared with wild-type mice on WD through activation of NF-κB, Stat3, JNK signaling pathways [38]
Chaperone-mediated autophagy (CMA): catabolic pathway for selective degradation of cytosolic proteins in lysosomes	Knockout mice 4–6 months old with selectively blocked CMA in liver	Key enzymes in carbohydrate and lipid metabolism are normally degraded by CMA while CMA block leads to peripheral adiposity, increased energy expenditure, and altered glucose homeostasis [39]