Glucagon-like peptide 1 and exendin-4 convert pancreatic AR42J cells into glucagon- and insulin-producing cells.
In this article, we show that glucagon-like peptide 1 (GLP-1) can induce AR42J cells to differentiate into insulin, pancreatic polypeptide, and glucagon-positive cells. In their natural state, these cells, which are derived from a chemically induced pancreatic tumor, possess exocrine and neuroendocrine properties but are negative for islet hormones and their mRNAs. We found that when these cells were exposed to GLP-1 (1 or 10 nmol), a peptide normally released from the gut in response to food and a modulator of insulin release, intracellular cAMP levels were increased, and proliferation of cells was increased for the first 24 h, followed by inhibition. Up to 50% of the cells became positive for islet hormones. The mRNAs for glucose transporter 2 and glucokinase were detected in the GLP-1-treated cells. Insulin was detected by radioimmunoassay (RIA) in the medium of GLP-1-treated cells, and the cells were capable of releasing insulin in a glucose-mediated fashion. Exendin-4, an analog of GLP-1, in some critical experiments performed in a similar manner to GLP-1, with the exception of it being 10-fold more potent. We therefore propose that GLP-1 and exendin-4 are capable of causing pancreatic precursor cells to differentiate into islet cells.
Zhou
J
J
Diabetes Section, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
Wang
X
X
Pineyro
M A
MA
Egan
J M
JM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000681:Amylases / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002766:Cholecystokinin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D000077270:Exenatide; D005786:Gene Expression Regulation; D005934:Glucagon / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics*; D007700:Kinetics; D010190:Pancreatic Neoplasms; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014688:Venoms / Q000494:pharmacology
D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D014688:Venoms; D003907:Dexamethasone; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D002766:Cholecystokinin; D000077270:Exenatide; D000681:Amylases; D000262:Adenylyl Cyclases