Using transcriptome tools and mouse models of insulin resistance, in this study we show: a) that mechanisms of proliferation and survival signals were downregulated in POKO islets from an early age, b) we also identified new pathways that could be involved in the adaptation of the β-cell to insulin resistance during obesity and that they are defective in PPARγ-deficient ob/ob islets. Here, PPARG is linked to obesity disorder.