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 beta-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 beta-geo fusion gene encoding beta-galactosidase reporter activity. Here we show that no 5-bromo-4-chloro-3-indolyl-ss-d-galactopyranoside (X-gal) staining was observed in islet beta-cells derived from Paskin knockout mice, irrespective of the ambient glucose concentration, whereas adenoviral expression of the lacZ gene in beta-cells showed strong X-gal staining. No induction of PASKIN mRNA could be detected in insulinoma cell lines or in islet beta-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 beta-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 beta-cells and that glucose-stimulated insulin production is independent of PASKIN.
Borter
Emanuela
E
Institute of Physiology, University of Zürich, Zürich Center for Integrative Human Physiology, Switzerland.
Niessen
Markus
M
Zuellig
Richard
R
Spinas
Giatgen A
GA
Spielmann
Patrick
P
Camenisch
Gieri
G
Wenger
Roland H
RH
D000818:Animals; D018929:Cell Culture Techniques; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
D007328:Insulin; D012333:RNA, Messenger; C116037:PAS domain kinases; D017346:Protein Serine-Threonine Kinases; D005947:Glucose