FIG. 5.

β-cell can transfer glucotoxicity and lipotoxicity toward inflammation. Glucose can lead to the TXNIP-initiated NLRP3 inflammasome assembly even in pancreatic β-cells, which is also activated upon the ER stress. This can increase expression and excretion of interleukins, such as IL-1β. Paracrine or autocrine action of IL-1β stimulates interleukin-1 receptor-1 (IL-1R1) signaling further revolving the oxidative stress and proapoptotic state. Lipotoxic FAs via TLR2 and TLR4 can stimulate both inflammasome formation and NF-κB signaling, initiating besides other factors, fetuin and chemokines. These provide signals for macrophage recruitment and concomitant islet inflammation. Hypothetically, these signals can be relayed up to periphery to induce insulin resistance. IL, interleukin; IL-1β, interleukin-1β; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NLRP, NOD-like receptor containing pyrin domain; TLR, toll-like receptor; TXNIP, thioredoxin interacting protein.