Epinephrine-induced hyperpolarization of pancreatic islet cells is sensitive to PI3K-PDK1 signaling.
Epinephrine inhibits insulin release by activation of K(+) channels and subsequent hyperpolarization of pancreatic beta cells. The present study explored whether epinephrine-induced hyperpolarization is modified by phosphatidylinositol 3-kinase (PI3K) and phosphatidylinositide-dependent kinase PDK1. Perforated patch-clamp was performed in islet cells isolated from PDK1 hypomorphic mice (pdk1(fl/fl)), expressing only 20% of PDK1, and in their wild-type littermates. At 16.8mM glucose, the cell membrane was hyperpolarized by epinephrine (1 microM), an effect significantly blunted in pdk1(fl/fl) and abrogated in wild-type cells by inhibition of PI3K with wortmannin (100 nM) or LY294002 (10 microM). The hyperpolarizing effect of epinephrine in pancreatic islet cells is thus sensitive to PI3K and PDK1.
Zhang
Ying
Y
Institute of Physiology, University of Tübingen, Gmelinstrasse 5, D-72076 Tübingen, Germany.
Shumilina
Ekaterina
E
Häring
Hans-Ulrich
HU
Lang
Florian
F
Ullrich
Susanne
S
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D004837:Epinephrine / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D007515:Islets of Langerhans / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D008817:Mice, Mutant Strains; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction
D064413:3-Phosphoinositide-Dependent Protein Kinases; D004837:Epinephrine; D005947:Glucose; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; C578564:Pdpk1 protein, mouse