CaV2.3 channel and PKCλ: new players in insulin secretion
Shao-Nian Yang, Per-Olof Berggren
Shao-Nian Yang, Per-Olof Berggren
Published January 3, 2005
Citation Information: J Clin Invest. 2005;115(1):16-20. https://doi.org/10.1172/JCI23970.
View: Text | PDF
Commentary

CaV2.3 channel and PKCλ: new players in insulin secretion

Abstract

Insulin secretion is critically dependent on the proper function of a complex molecular network. CaV2.3-knockout (CaV2.3–/–) and PKCλ-knockout (PKCλ–/–) mouse models now suggest that these 2 players, the Cav2.3 channel and PKCλ, are important constituents of this molecular network. Subsequent to glucose stimulation, insulin is released from the pancreatic β cell in a biphasic pattern, i.e., a rapid initial phase followed by a slower, more sustained phase. Interestingly, Ca2+ influx through the CaV2.3 channel regulates only the second phase of insulin secretion. PKCλ seems to enter the β cell nucleus and in turn modulates the expression of several genes critical for β cell secretory function. Studies by Hashimoto et al. and Jing et al. in this issue of the JCI set out to answer the question of why numerous isoforms of proteins with similar functions are present in the β cell. This is important, since it has been difficult to understand the modulatory and/or regulatory roles of different isoforms of proteins in defined subcellular compartments and at various times during the secretory process in both β cell physiology and pathophysiology.

Authors

Shao-Nian Yang, Per-Olof Berggren

×

Figure 2

Options: View larger image (or click on image) Download as PowerPoint
Ten isoforms of PKC with closely related kinase domains are classified i...
Ten isoforms of PKC with closely related kinase domains are classified into 3 subgroups: conventional PKC isoforms (PKCα, PKCβI, PKCβII, and PKCγ), novel PKC isoforms (PKCδ, PKCε, PKCη, and PKCθ), and atypical PKC isoforms (PKCζ and PKCι/λ). Multiple conventional PKC and novel PKC isoforms (c/n PKC) are involved in the regulation of insulin secretion through different targets. PKCλ in the β cell is now shown to participate in glucose-stimulated insulin secretion by modulating the expression of HNF3β, hexokinase 1, hexokinase 2, glucose transporter 2, Kir6.2, and Sur1 subunit genes critical for β cell function. G, GTP-binding protein; GR, GTP-binding protein–coupled receptors; P, phosphoryl group; PB1, Phox and Bem 1; PDK-1, phosphatidylinositol 3-kinase-dependent kinase–1; PIP2, phosphatidylinositol 4,5-bisphosphate; PIP3, phosphatidylinositol 3,4,5-trisphosphate; PLC, phospholipase C; TKR, tyrosine kinase receptor.