Cell type-specific deletion in mice reveals roles for PAS kinase in insulin and glucagon production

Aims/hypothesis Per-Arnt-Sim kinase (PASK) is a nutrient-regulated domain-containing protein kinase previously implicated in the control of insulin gene expression and glucagon secretion. Here, we explore the roles of PASK in the control of islet hormone release, by generating mice with selective deletion of the Pask gene in pancreatic beta or alpha cells. Methods Floxed alleles of Pask were produced by homologous recombination and animals bred with mice bearing beta ( Ins1 Cre ; Pask BKO) or alpha ( Ppg Cre [also known as Gcg ]; Pask AKO) cell-selective Cre recombinase alleles. Glucose homeostasis and hormone secretion in vivo and in vitro, gene expression and islet cell mass were measured using standard techniques. Results Ins1 Cre -based recombination led to efficient beta cell-targeted deletion of Pask . Beta cell mass was reduced by 36.5% ( p