Galanin and epinephrine act on distinct receptors to inhibit insulin release by the same mechanisms including an increase in K+ permeability of the B-cell membrane.
The mechanisms by which galanin and epinephrine affect pancreatic B-cell function were studied in normal mouse islets. In the presence of 15 mM glucose and 2.5 mM Ca2+, galanin (50 nM) and epinephrine (100 nM) hyperpolarized the B-cell membrane and suppressed electrical activity only transiently. These changes were accompanied by a decrease in 86Rb+ efflux from islet cells and nearly complete inhibition of insulin release. Both agents also decreased 86Rb+ efflux in the absence of Ca2+. Low concentrations (10-15 microM) of diazoxide, an activator of ATP-sensitive K+ channels, mimicked some effects of galanin and epinephrine. However, insulin release was more markedly inhibited by galanin or epinephrine than by diazoxide when electrical activity was similarly decreased, and diazoxide had no effect on 86Rb+ efflux in the absence of Ca2+. When the permeability to K+ was increased by 100 microM diazoxide and the hyperpolarization reversed by high extracellular K+, galanin and epinephrine still inhibited insulin release, but did not affect the membrane potential or 86Rb+ efflux. Galanin and epinephrine decreased glucose utilization and oxidation in islet cells by about 10%, whereas diazoxide had no effect. Blockade of alpha 2-adrenoceptors by yohimbine suppressed the effects of epinephrine, but not those of galanin. It is concluded that activation of galanin and alpha2-adrenergic receptors inhibits insulin release by the same mechanisms. These may involve an increase in K+ permeability of the B-cell membrane by opening ATP-sensitive K+ channels and an additional effect independent of the membrane potential.
Drews
G
G
I Physiologisches Institut, University of Saarland, Homburg/Saar, West Germany.
Debuyser
A
A
Nenquin
M
M
Henquin
J C
JC
D000818:Animals; D001696:Biomechanical Phenomena; D002463:Cell Membrane Permeability; D003981:Diazoxide / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D019004:Galanin; D007329:Insulin Antagonists / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012413:Rubidium / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
D007329:Insulin Antagonists; D010455:Peptides; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D019004:Galanin; D012413:Rubidium; D003981:Diazoxide; D011188:Potassium; D004837:Epinephrine