Electrical activity, cAMP concentration, and insulin release in mouse islets of Langerhans.
The influence of forskolin and 3-iso-butyl-1-methylxanthine (IBMX) on mouse pancreatic beta-cell electrical activity, whole islet cAMP content, and insulin release were investigated. The two drugs potentiated to a similar extent both glucose-stimulated electrical activity and insulin release. In terms of the electrical response, both drugs potentiated the silent depolarization of the membrane in response to low (substimulatory) glucose concentrations, whereas at higher (stimulatory) glucose concentrations they caused an increase in the plateau fraction, with a response similar to the effect of increasing the glucose concentration. Both phases of insulin release were increased by each of the drugs. Ten micromolar forskolin and 100 microM IBMX caused an increase in intraislet adenosine 3',5'-cyclic monophosphate (cAMP) in the presence of 11.1 mM glucose, the former a 17-fold and the latter a 2-fold increase over the cAMP concentration in the presence of glucose alone. Because the two drugs lead to an increase in islet cAMP content, it is proposed that protein phosphorylation resulting from an activation of beta-cell cAMP-dependent protein kinases is responsible for the potentiation of the glucose-induced insulin release and beta-cell electrical activity. The observed effects on electrical activity are compatible with the hypothesis that cAMP-dependent phosphorylation induces alteration of the kinetics of the calcium-sensitive potassium permeability of the beta-cell plasma membrane. The increase in calcium entry into the beta-cell that would result from these alterations may be responsible for the cAMP-dependent potentiation of insulin release.
Eddlestone
G T
GT
Oldham
S B
SB
Lipson
L G
LG
Premdas
F H
FH
Beigelman
P M
PM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin; D000242:Cyclic AMP / Q000502:physiology*; D004224:Diterpenes / Q000494:pharmacology; D004553:Electric Conductivity / Q000187:drug effects; D005947:Glucose / 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; D051379:Mice
D004224:Diterpenes; D007328:Insulin; D005576:Colforsin; D003994:Bucladesine; D000242:Cyclic AMP; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine