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

Emanuela Borter1, Markus Niessen, Richard Zuellig

  • 1Institute of Physiology, University of Zürich, Zürich Center for Integrative Human Physiology, Switzerland.

Diabetes
|December 29, 2006
PubMed

Insights

PASKIN kinase is not induced by glucose in pancreatic beta-cells. Glucose-stimulated insulin production and blood glucose regulation are independent of PASKIN, challenging previous findings.

Area of Science:

  • Cellular metabolism
  • Endocrinology
  • Molecular biology

Background:

  • The Per-ARNT-Sim (PAS) domain serine/threonine kinase PASKIN links energy flux and protein synthesis.
  • Previous studies suggested PASKIN is upregulated by hyperglycemia and essential for insulin gene expression in pancreatic beta-cells.

Purpose of the Study:

  • To investigate the role of PASKIN in glucose-stimulated insulin production and regulation of blood glucose.
  • To validate the regulation of PASKIN by glucose in pancreatic beta-cells.

Main Methods:

  • Generation of Paskin knockout mice using a beta-geo fusion gene.
  • Analysis of X-gal staining in beta-cells from knockout and wild-type mice.
  • Measurement of PASKIN mRNA levels in insulinoma cell lines and primary beta-cells.
  • Assessment of insulin mRNA levels and insulin release under varying glucose concentrations.
  • Evaluation of blood glucose levels and glucose tolerance in Paskin knockout and wild-type mice.

Main Results:

  • Paskin knockout mice exhibited no X-gal staining in beta-cells, indicating successful gene knockout.
  • PASKIN mRNA levels were not induced by glucose in insulinoma cell lines or primary beta-cells.
  • Insulin mRNA levels and insulin release were induced by glucose independently of PASKIN.
  • PASKIN mRNA was abundant in testes but undetectable in the pancreas and beta-cells.
  • Paskin knockout and wild-type mice showed no significant differences in blood glucose levels or glucose tolerance.

Conclusions:

  • Paskin gene expression is not regulated by glucose in pancreatic beta-cells.
  • Glucose-stimulated insulin production and glucose homeostasis are independent of PASKIN.
  • The previously reported role of PASKIN in hyperglycemia-induced insulin gene expression requires re-evaluation.

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