Glucose-stimulated insulin production in mice deficient for the PAS kinase PASKIN

The Per-ARNT-Sim (PAS) domain serine/threonine kinase PASKIN, or PAS kinase, links energy flux and protein synthesis in yeast and regulates glycogen synthase in mammals. A recent report suggested that PASKIN mRNA, protein, and kinase activity are increased in pancreatic islet β-cells under hyperglycemic conditions and that PASKIN is necessary for insulin gene expression. We previously generated Paskin knockout mice by targeted replacement of the kinase domain with the β-geo fusion gene encoding β-galactosidase reporter activity. Here we show that no 5-bromo-4-chloro-3-indolyl-β-D-galactopyranoside (X-gal) staining was observed in islet β-cells derived from Paskin knockout mice, irrespective of the ambient glucose concentration, whereas adenoviral expression of the lacZ gene in β-cells showed strong X-gal staining. No induction of PASKIN mRNA could be detected in insulinoma cell lines or in islet β-cells. Increasing glucose concentrations resulted in PASKIN-independent induction of insulin mRNA levels and insulin release. PASKIN mRNA levels were high in testes but undetectable in pancreas and in islet β-cells. Finally, blood glucose levels and glucose tolerance after intraperitoneal glucose injection were indistinguishable between Paskin wild-type and knockout mice. These results suggest that Paskin gene expression is not induced by glucose in pancreatic β-cells and that glucose-stimulated insulin production is independent of PASKIN.
The Per-ARNT-Sim (PAS) domain proteins often serve as environment sensors, regulating the cellular metabolism and behavior of microorganisms in response to, among others, oxygen or light. In nitrogen-fixing Rhizobium species, [...]