show Abstracthide AbstractProgressive reductions in ß-cell mass and function comprise the core of the pathogenesis mechanism leading to type 2 diabetes (T2D). To understand the molecular events in this process, we quantified the temporal transcriptome and proteome of pancreatic islets from Goto-Kakizaki (GK) rats at different stages of diabetes. Integrated omics analysis allowed us to unravel the chronological order of T2D-related molecular events during GK islet deterioration. Two major events occur early in the disease, specifically, a reduction in ß-cell mass caused by defective neogenesis and senescence-related low proliferation, and metabolic shift caused by mitochondrial dysfunction. Furthermore, our data revealed the evolution of compensation failure in GK islets and two distinct stages of islet inflammation: priming and amplification. Our study offers a valuable resource for the diabetes research community and will facilitate further studies aimed at protecting ß-cell mass and function. Overall design: We performed a time-course large-scale transcriptome of pancreatic islets in GK male rats vs control, age-matched WST male rats at five time points (week 4, 6, 8, 16 and 24) using MAPS method