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 AR 42J cells to differentiate into insulin, pancreatic polypeptide, and glucag on-positive cells. In their natural state, these cells, which are derived f rom a chemically induced pancreatic tumor, possess exocrine and neuroendocr ine properties but are negative for islet hormones and their mRNAs, We foun d that when these cells were exposed to GLP-1 (1 or 10 nmol), a peptide nor mally released from the gut in response to food and a modulator of insulin release, intracellular cAMP levels mere increased, and proliferation of cel ls was increased for the first 24 h, followed by inhibition, Up to 50% of t he cells became positive for islet hormones. The mRNAs for glucose transpor ter 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, a nd the cells were capable of releasing insulin in a glucose-mediated fashio n. 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 pot ent. We therefore propose that GLP-1 and exendin-4 are capable of causing p ancreatic precursor cells to differentiate into islet cells.