Enhanced insulin sensitivity of gene-targeted mice lacking functional KCNQ1. Academic Article uri icon


  • The pore-forming K+-channel alpha-subunit KCNQ1 is expressed in a wide variety of tissues including heart, skeletal muscle, liver, and epithelia. Most recent evidence revealed an association of the KCNQ1 gene with the susceptibility to type 2 diabetes. KCNQ1 participates in the regulation of cell volume, which is, in turn, critically important for the regulation of metabolism by insulin. The present study explored the influence of KCNQ1 on insulin-induced cellular K+ uptake and glucose metabolism. Insulin (100 nM)-induced K+ uptake was determined in isolated perfused livers from KCNQ1-deficient mice (kcnq1(-/-)) and their wild-type littermates (kcnq1(+/+)). Moreover, plasma glucose and insulin levels, intraperitoneal glucose (3 g/kg) tolerance, insulin (0.15 U/kg)-induced hypoglycemia, and peripheral uptake of radiolabeled 3H-deoxy-glucose were determined in both genotypes. Insulin-stimulated hepatocellular K+ uptake was significantly more sustained in isolated perfused livers from kcnq1(-/-) mice than from kcnq1(+/+)mice. The decline of plasma glucose concentration following an intraperitoneal injection of insulin was again significantly more sustained in kcnq1(-/-) than in kcnq1(+/+) mice. Both fasted and nonfasted plasma glucose and insulin concentrations were significantly lower in kcnq1(-/-) than in kcnq1(+/+)mice. Following an intraperitoneal glucose injection, the peak plasma glucose concentration was significantly lower in kcnq1(-/-) than in kcnq1(+/+)mice. Uptake of 3H-deoxy-glucose into skeletal muscle, liver, kidney and lung tissue was significantly higher in kcnq1(-/-) than in kcnq1(+/+)mice. In conclusion, KCNQ1 counteracts the stimulation of cellular K+ uptake by insulin and thereby influences K+-dependent insulin signaling on glucose metabolism. The observations indicate that KCNQ1 is a novel molecule affecting insulin sensitivity of glucose metabolism.

published proceedings

  • Am J Physiol Regul Integr Comp Physiol

author list (cited authors)

  • Boini, K. M., Graf, D., Hennige, A. M., Koka, S., Kempe, D. S., Wang, K., ... Lang, F.

citation count

  • 50

complete list of authors

  • Boini, Krishna M||Graf, Dirk||Hennige, Anita M||Koka, Saisudha||Kempe, Daniela S||Wang, Kan||Ackermann, Teresa F||Föller, Michael||Vallon, Volker||Pfeifer, Karl||Schleicher, Erwin||Ullrich, Susanne||Häring, Hans-Ulrich||Häussinger, Dieter||Lang, Florian

publication date

  • June 2009