Correlation of the activation of Ca2+/calmodulin-dependent protein kinase II with the initiation of insulin secretion from perifused pancreatic islets.
An experimental procedure has been designed to permit the simultaneous assessment of the activation status of the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) with insulin secretion in perifused islets. By this procedure, the activation of CaM kinase II by glucose correlated closely with the initial and sustained phases of insulin secretion within a 30-min test period. By contrast, islets (160-200/tube) in static incubations neither supported second-phase insulin secretion nor CaM kinase II activation beyond 10-15 min. This was not the result of the accumulation of insulin, because the introduction of insulin (40-160 ng/ml) into the perifusion medium failed to mimic the suppression of glucose-induced insulin secretion or CaM kinase II activation. A similar addition of SRIF (0.01-1 microM) or epinephrine (1 microM) profoundly suppressed insulin secretion although failing to significantly influence CaM kinase II activation. Finally, on withdrawal of glucose from perifused islets, insulin secretion rapidly returned to basal rates, but CaM kinase II deactivation was significantly delayed. The correlation of kinase activation with the initiation of insulin secretion suggests that CaM kinase II may be important in the regulation of glucose-induced insulin secretion. The observed dissociation of these parameters in the presence of inhibitory hormones or after the withdrawal of a glucose stimulus, however, suggests that the kinase is not directly involved in the final steps of insulin exocytosis.
Easom
R A
RA
Department of Biochemistry and Molecular Biology, University of North Texas Health Science Center at Fort Worth, 76107-2699, USA. reasom@hsc.unt.edu
Filler
N R
NR
Ings
E M
EM
Tarpley
J
J
Landt
M
M
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000494:pharmacology; D013997:Time Factors
D007328:Insulin; D013004:Somatostatin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005947:Glucose; D004837:Epinephrine