抄録
Introduction : GLP-1, a cAMP mobilizing agonist, is an insulinotropic peptide released from the intestinal L cell in response to a meal. However, the underlying mechanisms of the stimulatory effect of GLP-1 on insulin secretion remain fully elucidated. Aim: The present study was conducted to examine whether GLP-1 can activate PKCalpah and PKCepsilon in INS-1 cells at a substimulatory concentration of glucose. Methods: We employed either GFP or DsRed-tagged proteins related to PKC signaling pathway using epifluorescence microscopy and total internal reflection fluorescence microscopy. Results: We first showed that GLP-1 translocated endogenous PKCalpah and PKCepsilon from the cytosol to the plasma membrane. Then we assessed the phosphorylation state of the PKC substrate, myristoylated alanine-rich C kinase substrate (MARCKS), as a maker of PKC activation. GLP-1 translocated GFP-tagged MARCKS from the plasma membrane to the cytosol and the GLP-1-evoked translocation of MARCKS-GFP was blocked by PKC inhibitors. The above observations were verified in three different ways using live cell imaging technique.In addition to these results, PKC inhibitors reduced forskolin-induced insulin secretion in INS-1 cells and rat islet beta cells. Conclusion: GLP-1 can activate PKCalpah and PKCepsilon, and the GLP-1-activated PKCs may contribute considerably to insulin secretion at a substimulatory concentration of glucose. [J Physiol Sci. 2006;56 Suppl:S67]
