Conophylline and betacellulin-δ4: An effective combination of differentiation factors for pancreatic β cells

Ryu Ichi Kitamura, Takeki Ogata, Yuji Tanaka, Kazuo Motoyoshi, Masaharu Seno, Izumi Takei, Kazuo Umezawa, Itaru Kojima

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Conophylline and betacellulin-δ4 reproduce differentiation-inducing activity of activin A and betacellulin, respectively. We examined the effect of conophylline and betacellulin-δ4 on β cell differentiation. In AR42J cells, conophylline and betacellulin-δ4 converted them into insulin-producing cells. Cells treated with conophylline and betacellulin-δ4 continued to grow after differentiation. Thus, cell number and insulin content were much greater compared to cells treated with activin A and betacellulin. Furthermore, cells treated with conophylline and betacellulin-δ4 secreted insulin in response to glucose. Likewise, conophylline and betacellulin-δ4 converted pancreatic ductal cells into insulin-producing cells. Insulin content, cell number and glucose-evoked insulin secretion were significantly greater than those in cells treated with activin A and betacellulin. Transplantation of pseudoislets prepared using ductal cells treated with conophylline and betacellulin-δ4 was able to reduce effectively the plasma glucose concentration in streptozotocin-treated nude mice. Conophylline and betacellulin-δ4 are effective in inducing differentiation of β cells from progenitors.

Original languageEnglish
Pages (from-to)255-264
Number of pages10
JournalEndocrine journal
Volume54
Issue number2
DOIs
Publication statusPublished - May 29 2007

Keywords

  • Differentiation
  • Insulin
  • Pancreatic β cell
  • Progenitor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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    Kitamura, R. I., Ogata, T., Tanaka, Y., Motoyoshi, K., Seno, M., Takei, I., Umezawa, K., & Kojima, I. (2007). Conophylline and betacellulin-δ4: An effective combination of differentiation factors for pancreatic β cells. Endocrine journal, 54(2), 255-264. https://doi.org/10.1507/endocrj.K06-199