The imidazoline RX871024 stimulates insulin secretion in pancreatic beta-cells from mice deficient in K(ATP) channel function.
Effects of the imidazoline compound RX871024 on cytosolic free Ca(2+) concentration ([Ca(2+)]i) and insulin secretion in pancreatic beta-cells from SUR1 deficient mice have been studied. In beta-cells from wild-type mice RX871024 increased [Ca(2+)]i by blocking ATP-dependent K(+)-current (K(ATP)) and inducing membrane depolarization. In beta-cells lacking a component of the K(ATP)-channel, SUR1 subunit, RX871024 failed to increase [Ca(2+)]i. However, insulin secretion in these cells was strongly stimulated by the imidazoline. Thus, a major component of the insulinotropic activity of RX871024 is stimulation of insulin exocytosis independently from changes in K(ATP)-current and [Ca(2+)]i. This means that effects of RX871024 on insulin exocytosis are partly mediated by interaction with proteins distinct from those composing the K(ATP)-channel.
Efanov
A M
AM
Rolf Luft Center for Diabetes Research, Karolinska Hospital, Stockholm, 17176, Sweden.
Høy
M
M
Bränström
R
R
Zaitsev
S V
SV
Magnuson
M A
MA
Efendic
S
S
Gromada
J
J
Berggren
P O
PO
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011401:Promoter Regions, Genetic; D012016:Reference Values; D014982:Xenopus laevis
C101943:2-(2-imidazolin-2-yl)-1-phenyl-1H-indole; D007093:Imidazoles; D007211:Indoles; D007328:Insulin; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D002118:Calcium