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.
Yamasaki
K
K
Department of Internal Medicine (III), Jikei University School of Medicine.
Sasaki
T
T
Nemoto
M
M
Eto
Y
Y
Tajima
N
N
D016475:3T3 Cells; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D045683:Furin; D005818:Genetic Engineering; D015316:Genetic Therapy; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D051379:Mice; D011384:Proinsulin / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013381:Subtilisins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D018076:DNA, Complementary; D007328:Insulin; D012333:RNA, Messenger; D011384:Proinsulin; D013381:Subtilisins; D045683:Furin