When AR42J cells, an amylase-secreting pancreatic exocrine cell line, were treated with activin A, cells extended neuritelike processes, and, concomitantly, amylase-containing vesicles disappeared. Immunofluorescence and immunoelectron microscopy revealed that these processes had neurite-specific cytoskeletal architectures: neurofilaments and microtubule bundles with cross-bridges of microtubule-associated protein 2. In addition to such morphological changes, activin-treated cells exhibited a marked increase in cytoplasmic free calcium concentration in response to depolarizing concentration of potassium. Moreover, activin-treated AR42J cells expressed mRNA for alpha 1 subunit of the neuroendocrine/beta cell-type voltage-dependent calcium channel. In naive AR42J cells, a sulfonylurea compound, tolbutamide, did not affect free calcium concentration, while it induced a marked elevation of free calcium in activin-treated cells. Single channel recording of the membrane patch revealed the existence of ATP-sensitive potassium channel in activin-treated cells. These results indicate that activin A converts amylase-secreting AR42J cells to neuronlike cells. Given that pancreatic endocrine cells possess neuronlike properties and express ATP-sensitive potassium channel as well as neuroendocrine/beta cell-type voltage-dependent calcium channel, activin treatment of AR42J cells may provide an in vitro model system to study the conversion of pancreatic exocrine cells to endocrine cells in islets.
H Ohnishi, N Ohgushi, S Tanaka, H Mogami, R Nobusawa, H Mashima, M Furukawa, T Mine, O Shimada, H Ishikawa
Title and authors | Publication | Year |
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Expression of Progenitor Cell Markers During Expansion of Sorted Human Pancreatic Beta Cells
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Id3 modulates cellular localization of bHLH Ptf1-p48 protein
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2009 | |
Nodal and lefty signaling regulates the growth of pancreatic cells
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Developmental Dynamics | 2008 |
Up-Regulation of JAM-1 in AR42J Cells Treated with Activin A and Betacellulin and the Diabetic Regenerating Islets
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Activin A Decreases glucagon and arx Gene Expression in α-Cell Lines
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Molecular Endocrinology | 2007 |
Therapeutic Potential of Follistatin to Promote Tissue Regeneration and Prevent Tissue Fibrosis
F AOKI, I KOJIMA |
Endocrine Journal | 2007 |
Conophylline: A novel differentiation inducer for pancreatic β cells
I Kojima, K Umezawa |
The International Journal of Biochemistry & Cell Biology | 2006 |
Hepatocyte progenitors in man and in rodents – multiple pathways, multiple candidates
J Laurson, C Selden, HJ Hodgson |
International Journal of Experimental Pathology | 2005 |
Roles of CTPL/Sfxn3 and Sfxn family members in pancreatic islet
Y Yoshikumi, H Mashima, N Ueda, H Ohno, J Suzuki, S Tanaka, M Hayashi, N Sekine, H Ohnishi, H Yasuda, T Iiri, M Omata, T Fujita, I Kojima |
Journal of Cellular Biochemistry | 2005 |
Expression of progenitor cell markers during expansion of sorted human pancreatic beta cells
Thomas Bouckenooghe, Brigitte Vandewalle, Ericka Moerman, Pierre-Marie Danzé, Bruno Lukowiak, Ghaffar Muharram, Julie Kerr-Conte, Valery Gmyr, Bernard Laine, François Pattou |
Gene expression | 2005 |
Involvement of syntaxin 4 in the transport of membrane-type 1 matrix metalloproteinase to the plasma membrane in human gastric epithelial cells
T Miyata, H Ohnishi, J Suzuki, Y Yoshikumi, H Ohno, H Mashima, H Yasuda, T Ishijima, H Osawa, K Satoh, K Sunada, H Kita, H Yamamoto, K Sugano |
Biochemical and Biophysical Research Communications | 2004 |
Angiotensin II stimulates DNA synthesis of rat pancreatic stellate cells by activating ERK through EGF receptor transactivation
K Hama, H Ohnishi, H Yasuda, N Ueda, H Mashima, Y Satoh, K Hanatsuka, H Kita, A Ohashi, K Tamada, K Sugano |
Biochemical and Biophysical Research Communications | 2004 |
Screening of bioactive metabolites for pancreatic regeneration chemotherapy
H Takatsuna, K Umezawa |
Biomedicine & Pharmacotherapy | 2004 |
Influence of systematically varied nanoscale topography on the morphology of epithelial cells
A Andersson, J Brink, U Lidberg, DS Sutherland |
IEEE Transactions on Nanobioscience | 2003 |
Induction of insulin production in rat pancreatic acinar carcinoma cells by conophylline
K Umezawa, A Hiroki, M Kawakami, H Naka, I Takei, T Ogata, I Kojima, T Koyano, T Kowithayakorn, HS Pang, TS Kam |
Biomedicine & Pharmacotherapy | 2003 |
A Novel Mitochondrial Ca 2+ -dependent Solute Carrier in the Liver Identified by mRNA Differential Display
H Mashima, N Ueda, H Ohno, J Suzuki, H Ohnishi, H Yasuda, T Tsuchida, C Kanamaru, N Makita, T Iiri, M Omata, I Kojima |
The Journal of biological chemistry | 2003 |
Regulation of Pax4 Paired Homeodomain Gene by Neuron-restrictive Silencer Factor
DM Kemp, JC Lin, JF Habener |
The Journal of biological chemistry | 2003 |
Effects of Selective Endocrine or Exocrine Induction of AR42J on SNARE and Munc18 Protein Expression
X Huang, L Sheu, Y Kang, Y Eto, I Kojima, HY Gaisano |
Pancreas | 2002 |
Expression of a Novel Zinc-Finger cDNA, IA-1, Is Associated with Rat AR42J Cells Differentiation into Insulin-Positive Cells
M Zhu, MB Breslin, MS Lan |
Pancreas | 2002 |
Brn-4 Transcription Factor Expression Targeted to the Early Developing Mouse Pancreas Induces Ectopic Glucagon Gene Expression in Insulin-producing β Cells
MA Hussain, CP Miller, JF Habener |
The Journal of biological chemistry | 2002 |
Up-Regulation of the Expression of Activins in the Pancreatic Duct by Reduction of the β-Cell Mass
YQ Zhang, H Zhang, A Maeshima, H Kurihara, J Miyagawa, T Takeuchi, I Kojima |
Endocrinology | 2002 |
Promotion of β-Cell Regeneration by Betacellulin in Ninety Percent-Pancreatectomized Rats
L Li, M Seno, H Yamada, I Kojima |
Endocrinology | 2001 |
Molecular Cloning of a Novel Brain-Type Na+-Dependent Inorganic Phosphate Cotransporter
Y Aihara, H Mashima, H Onda, S Hisano, H Kasuya, T Hori, S Yamada, H Tomura, Y Yamada, I Inoue, I Kojima, J Takeda |
Journal of Neurochemistry | 2000 |
Immortalized Pancreatic Duct Cells in vitro and in vivo
R Jesnowski, P Muller, W Schareck, S Liebe, M Lohr |
Annals of the New York Academy of Sciences | 1999 |
Inhibin, Activin and Follistatin
T Aono, H Sugino, WW Vale |
1997 | |
Betacellulin and activin A coordinately convert amylase-secreting pancreatic AR42J cells into insulin-secreting cells
H Mashima, H Ohnishi, K Wakabayashi, T Mine, J Miyagawa, T Hanafusa, M Seno, H Yamada, I Kojima |
Journal of Clinical Investigation | 1996 |