BETACELLULIN AND ACTIVIN-A COORDINATELY CONVERT AMYLASE-SECRETING PANCREATIC AR42J CELLS INTO INSULIN-SECRETING CELLS

Rat pancreatic AR42J cells possess exocrine and neuroendocrine propert ies, Activin A induces morphological changes and converts them into ne uron-like cells. In activin-treated cells, mRNA for pancreatic polypep tide (PP) but not that for either insulin or glucagon was detected by reverse transcription-PCR. About 25% of the cells were stained by anti -PP antibody. When AR42J cells were incubated with betacellulin, a sma ll portion of the cells were stained positively with antiinsulin and a nti-PP antibodies, The effect of betacellulin was dose dependent, bein g maximal at 2 nM, Approximately 4% of the cells became insulin positi ve at this concentration, and mRNAs for insulin and PP were detected. When AR42J cells were incubated with a combination of betacellulin and activin A, similar to 10% of the cells became insulin positive, Morph ologically, the insulin-positive cells were composed of two types of c ells: neuron-like and round-shaped cells, Immunoreactive PP was found in the latter type of cells, The mRNAs for insulin, PP, glucose transp orter 2, and glucokinase, but not glucagon, were detected, Depolarizin g concentration of potassium, tolbutamide, carbachol, and glucagon-lik e peptide-1 stimulated the release of immunoreactive insulin, These re sults indicate that betacellulin and activin A convert amylase-secreti ng AR42J cells into cells secreting insulin. AR42J cells provide a mod el system to study the formation of pancreatic endocrine cells.