Differentiation-Induced Insulin Secretion from Nonendocrine Cells with Engineered Human Proinsulin cDNA

To investigate the effects of differentiation on insulin secretion from engineered nonendocrine cells, modified human proinsulin cDNA (INS/fur) was transfected to THP-1 monocyte and C2C12 myoblast cell lines. When THP-1 was differentiated into macrophages with phorbol ester, the insulin secretion rate was increased by 3.1-fold. This increase in insulin secretion is accompanied by a 17.6-fold increase in the processing efficiency of the modified human proinsulin and by a 3.5-fold increase in the abundance of furin mRNA. In addition, differentiation of C2C12 into myotubes, which can be induced by changing the serum, showed a 9.9-fold increase in insulin secretion and was accompanied by a 1.6-fold increase in the abundance of furin mRNA. The involvement of posttranslational processing and the exocytotic process in differentiation-induced insulin secretion could lead to the possibility of regulation of insulin secretion from genetically engineered cells.