Protein kinase activation increases insulin secretion by sensitizing the secretory machinery to Ca2+. J Gen Physiol 2004 Dec;124(6):653-62
Date
12/02/2004Pubmed ID
15572345Pubmed Central ID
PMC2234026DOI
10.1085/jgp.200409082Scopus ID
2-s2.0-10344258585 (requires institutional sign-in at Scopus site) 104 CitationsAbstract
Glucose and other secretagogues are thought to activate a variety of protein kinases. This study was designed to unravel the sites of action of protein kinase A (PKA) and protein kinase C (PKC) in modulating insulin secretion. By using high time resolution measurements of membrane capacitance and flash photolysis of caged Ca(2+), we characterize three kinetically different pools of vesicles in rat pancreatic beta-cells, namely, a highly calcium-sensitive pool (HCSP), a readily releasable pool (RRP), and a reserve pool. The size of the HCSP is approximately 20 fF under resting conditions, but is dramatically increased by application of either phorbol esters or forskolin. Phorbol esters and forskolin also increase the size of RRP to a lesser extent. The augmenting effect of phorbol esters or forskolin is blocked by various PKC or PKA inhibitors, indicating the involvement of these kinases. The effects of PKC and PKA on the size of the HCSP are not additive, suggesting a convergent mechanism. Using a protocol where membrane depolarization is combined with photorelease of Ca(2+), we find that the HCSP is a distinct population of vesicles from those colocalized with Ca(2+) channels. We propose that PKA and PKC promote insulin secretion by increasing the number of vesicles that are highly sensitive to Ca(2+).
Author List
Wan QF, Dong Y, Yang H, Lou X, Ding J, Xu TAuthor
Xuelin Lou PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCalcium
Calcium Channels
Calcium Signaling
Cells, Cultured
Enzyme Activation
Exocytosis
Insulin
Islets of Langerhans
Male
Protein Kinases
Rats
Rats, Wistar
Transport Vesicles