Beta-Cell Adaptation Unveiled: The Role of Myokines in Insulin Resistant mice. Related material.

Insulin resistance necessitates pancreatic beta cells adaptation to maintain glycemia. Beta-cell mass adaptation can occur via beta-cell proliferation or via beta-cell neogenesis (de novo beta-cell production). To clarify the specific contribution and mechanisms of beta-cell adaptation in response to insulin resistance; we took advantage of corticosterone-induced insulin resistance in young and old mice. We used quantitative 3D analysis of cleared whole pancreas immunostained for insulin. The bioinformatic pipeline and original code used for the 3D analysis is provided in the file "LibozBeaupere2024-MATLABscripts.zip". We find that insulin resistant myotubes can secrete factors that induce beta-cell differentiation, recapitulating in vitro a multi-organs crosstalk. Using a combination of RNA sequencing (Illumina, Novaseq6000, 150bp paired-end) and functional analysis on a pancreatic differentiation model, we demonstrate that 3 myokines stimulate beta-cell differentiation in vitro. RNAseq analyzed data (differentially expressed genes) from 3 independent biological replicates of corticosterone- or VEH-treated myotubes are provided in the file "Table2-DEG.xlsx", along with sequencing quality check "