Junctophilin 3 expresses in pancreatic beta cells and is required for glucose-stimulated insulin secretion.

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