Fig. 4

Overnutrition is responsible for elevated levels of glucose and FFAs in blood which entered into the β-cells of pancreatic islets. Initially, these augmented levels of glucose and FFAs induce the expression and release of IL-1β from the β-cells of pancreatic islets (Stimulation). Prolonged and/or chronic exposure of glucose and FFAs (also known as metabolic stress) may lead to the activation of IL-1β by activating NF-κB and auto-stimulatory process (Amplification). Once, IL-1β is activated and produced, it leads to the recruitment of various other pro-inflammatory cytokines, chemokines, and macrophages (Precipitation) which further induces apoptosis, amyloidosis and fibrosis in β-cells of pancreatic islets, and hence impaired insulin secretion occurs whereas, in peripheral tissues, IR is developed due to systemic inflammation. Adopted from Donath et al. [17]