Osteocalcin (OC), a bone-derived protein, affects the regulation of glucose and energy homeostasis in variety of target tissues. We previously reported that the number of cells expressing GLP-1 increased in peripheral cells of mouse pancreas by long-term administration of OC, and also in isolated pancreatic islets treated with OC.
In the present study, we examined the effect of OC on the expression of genes related to the property of pancreatic α cells. When, αTC1-6, a cultured pancreatic α cells were treated with OC, gene expression of prohormone convertase 1 (PC1/3), the enzyme necessary for the proteolytic processing of proglucagon to GLP-1, was elevated. On the other hand, OC downregulated the expression of pcsk1n, the gene for proSAAS, a specific endogenous inhibitor of PC1/3. Furthermore, the expression of transcriptional regulator pax6 was increased by OC-treatment of the cells. Since pax6 is known to down-regulate pcsk1n expression, these findings suggest that OC promotes GLP-1 production in pancreatic α cells by upregulating gene expression and increasing activity of the enzyme involved in proglucagon conversion to GLP-1 through pax6.