Glucose-Stimulated Insulin Production in Mice Deficient for the PAS Kinase PASKIN

  1. Emanuela Borter1,
  2. Markus Niessen2,
  3. Richard Zuellig2,
  4. Giatgen A. Spinas2,
  5. Patrick Spielmann1,
  6. Gieri Camenisch1 and
  7. Roland H. Wenger1
  1. 1Institute of Physiology and ZIHP (Zürich Center for Integrative Human Physiology), University of Zürich, Zürich, Switzerland
  2. 2Clinic for Endocrinology and Diabetes, University Hospital Zürich, University of Zürich, Zürich, Switzerland
  1. Address correspondence and reprint requests to Roland H. Wenger, Institute of Physiology, University of Zürich-Irchel, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. E-mail: roland.wenger{at}


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-ß-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 costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted October 13, 2006.
    • Received June 11, 2006.
| Table of Contents