title: Conophylline and betacellulin-delta4: an effective combination of differentiation factors for pancreatic beta cells.
abstract: Conophylline and betacellulin-delta4 reproduce differentiation-inducing activity of activin A and betacellulin, respectively. We examined the effect of conophylline and betacellulin-delta4 on beta cell differentiation. In AR42J cells, conophylline and betacellulin-delta4 converted them into insulin-producing cells. Cells treated with conophylline and betacellulin-delta4 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-delta4 secreted insulin in response to glucose. Likewise, conophylline and betacellulin-delta4 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-delta4 was able to reduce effectively the plasma glucose concentration in streptozotocin-treated nude mice. Conophylline and betacellulin-delta4 are effective in inducing differentiation of beta cells from progenitors.
authors.affiliation: Institute for Molecular and Cellular Regulation, Gunma University, Japan.
authors.forename: Ryu-Ichi
authors.initials: R
authors.lastname: Kitamura
authors.forename: Takeki
authors.initials: T
authors.lastname: Ogata
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kazuo
authors.initials: K
authors.lastname: Motoyoshi
authors.forename: Masaharu
authors.initials: M
authors.lastname: Seno
authors.forename: Izumi
authors.initials: I
authors.lastname: Takei
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
authors.forename: Itaru
authors.initials: I
authors.lastname: Kojima
mesh_terms: D000818:Animals; D066259:Betacellulin; D001786:Blood Glucose / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D017690:Cell Transplantation; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery; D004338:Drug Combinations; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010183:Pancreatic Ducts / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000166:cytology*; D014748:Vinca Alkaloids / Q000494:pharmacology*
chemical_list: D066259:Betacellulin; D001786:Blood Glucose; C587852:Btc protein, mouse; C587853:Btc protein, rat; D004338:Drug Combinations; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D014748:Vinca Alkaloids; C099167:conophylline; D005947:Glucose