PKCa is activated but not required during glucose-induced insulin secretion from rat pancreatic islets

Carpenter, L, Mitchell, C, Xu, Z, Poronnik, P, Both, G and Biden, T 2004, 'PKCa is activated but not required during glucose-induced insulin secretion from rat pancreatic islets', Diabetes, vol. 53, no. 1, pp. 53-60.


Document type: Journal Article
Collection: Journal Articles

Title PKCa is activated but not required during glucose-induced insulin secretion from rat pancreatic islets
Author(s) Carpenter, L
Mitchell, C
Xu, Z
Poronnik, P
Both, G
Biden, T
Year 2004
Journal name Diabetes
Volume number 53
Issue number 1
Start page 53
End page 60
Total pages 8
Publisher The American Diabetes Association
Abstract The role of protein kinase C (PKC) in glucose-stimulated insulin secretion (GSIS) is controversial. Using recombinant adenoviruses for overexpression of PKCa and PKCd, in both wild-type (WT) and kinase-dead (KD) forms, we here demonstrate that activation of these two PKCs is neither necessary nor sufficient for GSIS from batch-incubated, rat pancreatic islets. In contrast, responses to the pharmacologic activator 12-O-tetradecanoylphorbol-13-acetate (TPA) were reciprocally modulated by overexpression of the PKaWT or PKCaKD but not the corresponding PKCd adenoviruses. The kinetics of the secretory response to glucose (monitored by perifusion) were not altered in either cultured islets overexpressing PKCaKD or freshly isolated islets stimulated in the presence of the conventional PKC (cPKC) inhibitor Go6976. However, the latter did inhibit the secretory response to TPA. Using phosphorylation state-specific antisera for consensus PKC phosphorylation sites, we also showed that (compared with TPA) glucose causes only a modest and transient functional activation of PKC (maximal at 2-5 min). However, glucose did promote a prolonged (15 min) phosphorylation of PKC substrates in the presence of the phosphatase inhibitor okadaic acid. Overall, the results demonstrate that glucose does stimulate PKCa in pancreatic islets but that this makes little overall contribution to GSIS.
Subject Endocrinology
Keyword(s) animal cell
article
cell function
cell stimulation
concentration response
controlled study
enzyme activation
enzyme activity
enzyme phosphorylation
enzyme substrate
insulin release
male
nonhuman
pancreas islet
priority journal
protein expression
rat
DOI - identifier 10.2337/diabetes.53.1.53
ISSN 0012-1797
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