It is well accepted that junctophilin (JPHs) isoforms act as a physical bridge linking plasma membrane and endoplasmic reticulum (ER) for channel crosstalk in excitable cells. Our purpose is to investigate whether JPHs are involved in the proper communication between Ca2+ influx and subsequent Ca2+ amplification in pancreatic beta cells, thereby participating in regulating insulin secretion. The expression of JPH isoforms was examined in human and mouse pancreatic tissues, and JPH3 expression was found in both the beta cells. In mice, knockdown of Jph3 (si-Jph3) in islets decreased glucose-stimulated insulin secretion (GSIS) accompanied by mitochondrial function impairment. Si-Jph3 lowered the insulin secretory response to Ca2+ signaling in the presence of glucose, and reduced [Ca2+]c transient amplitude triggered by caffeine. Si-Jph3 also attenuated mitofusin 2 expression, thereby disturbing the spatial organization of ER–mitochondria contact in islets. These results suggest that the regulation of GSIS by the KATP channel-independent pathways is partly impaired due to decrease of JPH3 expression in mouse islets. JPH3 also binds to type 2 ryanodine receptors (RyR2) in mouse and human pancreatic tissues, which might contribute to Ca2+ release amplification in GSIS. This study demonstrates some previously unrecognized findings in pancreatic tissues: (1) JPH3 expresses in mouse and human beta cells; (2) si-Jph3 in mouse primary islets impairs GSIS in vitro; (3) impairment in GSIS in si-Jph3 islets is due to changes in RyR2-[Ca2+]c transient amplitude and ER-mitochondria contact.

The study was designed to examine the effects of calcitonin (CT) on the development of murine pre-implantation embryos and possible molecular mechanisms involved in the process. In the present study, the 2-cell embryos were treated with different concentration of CT in vitro for the indicated time and the results demonstrated that CT promoted the development of the pre-implantation embryos in a dosage-dependent manner by increasing the intracellular Ca(2+) level. Furthermore, the present study showed that CT significantly increased the expression of phospho-P38MAPK (Mitogen-Activated Protein Kinase) of the pre-implantation embryos by Western blots and pre-treatment of specific P38MAPK inhibitor significantly reduced the promotion effects of CT on the embryonic development in vitro culture. Moreover, the results of intrauterine horn injection showed that the average number of embryos implanted in CT-antibody or specific P38 MAPK inhibitor-treated uterus was significantly lower than that of the corresponding control, respectively. And the observation of tissue specimen suggested that some embryos were degenerated in CT-antibody or specific P38 MAPK inhibitor-treated uterus, and adipose vacuoles were present in the decidual cells. In conclusion, CT promoted the development of pre-implantation embryos and the intracellular Ca(2+) -dependent P38MAPK signal molecule was involved in the process.

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