Dual Role of Mitogen-Activated Protein Kinase 8 Interacting Protein-1 in Inflammasome and Pancreatic β-Cell Function.

Inflammasomes have been implicated in the pathogenesis of type 2 diabetes (T2D). However, their expression and functional importance in pancreatic β-cells remain largely unknown. Mitogen-activated protein kinase 8 interacting protein-1 (MAPK8IP1) is a scaffold protein that regulates JNK signaling and is involved in various cellular processes. The precise role of MAPK8IP1 in inflammasome activation in β-cells has not been defined. To address this gap in knowledge, we performed a set of bioinformatics, molecular, and functional experiments in human islets and INS-1 (832/13) cells. Using RNA-seq expression data, we mapped the expression pattern of proinflammatory and inflammasome-related genes (IRGs) in human pancreatic islets. Expression of in human islets was found to correlate positively with key IRGs, including the NOD-like receptor (NLR) family pyrin domain containing 3 (), Gasdermin D () and Apoptosis-associated speck-like protein containing a CARD (), but correlate inversely with Nuclear factor kappa 1 (), Caspase-1 (), Interleukin-18 (), Interleukin-1β () and Interleukin 6 (). Ablation of by siRNA in INS-1 cells down-regulated the basal expression levels of , NLR family CARD domain containing 4 (), NLR family CARD domain containing 1 (), , , , , , , and at the mRNA and/or protein level and decreased palmitic acid (PA)-induced inflammasome activation. Furthermore, -silened cells substantially reduced reactive oxygen species (ROS) generation and apoptosis in palmitic acid-stressed INS-1 cells. Nonetheless, silencing of failed to preserve β-cell function against inflammasome response. Taken together, these findings suggest that MAPK8IP1 is involved in regulating β-cells by multiple pathways.