Promotion of β-cell differentiation by the alkaloid conophylline in porcine pancreatic endocrine cells

• Published in: Biomedicine & pharmacotherapy Vol. 64; no. 3; pp. 226 - 231
• Main Authors: Kawakami, M, Hirayama, A, Tsuchiya, K, Ohgawara, H, Nakamura, M, Umezawa, K
• Format: Journal Article
• Language: English
• Published: France Elsevier SAS 01.03.2010
• Subjects: Animals; Animals, Newborn; Biomarkers; Cell Differentiation - drug effects; Cells, Cultured - drug effects; Conophylline; Diabetes mellitus; Drug Evaluation, Preclinical; Drug Synergism; Gene Expression Regulation - drug effects; Glucose - pharmacology; Insulin; Insulin - metabolism; Insulin Secretion; Internal Medicine; Islet-like cell clusters; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Medical Education; Molecular Structure; Niacinamide - pharmacology; Nicotinamide; Porcine pancreas; Reverse Transcriptase Polymerase Chain Reaction; Sus scrofa; Swine; Vinca Alkaloids - chemistry; Vinca Alkaloids - pharmacology; Conophylline; Nicotinamide; Porcine pancreas; Insulin; Islet-like cell clusters; Diabetes mellitus
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2009.09.025

Abstract We previously found that conophylline, an alkaloid isolated from the leaves of Ervatamia microphylla , induced β-cell differentiation in rat pancreatic acinar carcinoma cells and in cultured fetal rat pancreatic tissue and that it also decreased the blood glucose level in streptozotocin-treated fetal rats. In the present research, we looked into the effect of conophylline on the differentiation of newborn pig pancreatic endocrine cells into insulin-secreting cells. Conophylline potentiated the differentiation of monolayer cells into insulin-producing cells in the presence of nicotinamide in 3 weeks. Next we prepared islet-like cell clusters (ICC). Cononophylline together with nicotinamide also increased the number of insulin-producing cells and the insulin content in ICC in 3–6 weeks. The ICC thus prepared were sensitive to the glucose concentration for the insulin secretion. Conophylline increased the mRNA expression of PDX-1, neurogenin3, neuroD/Beta2, and insulin in ICC. Thus, the vinca alkaloid conophylline potentiated β-cell differentiation in porcine pancreatic endocrine-rich cells in cluster cultures. Pig pancreatic cells are practical candidate for use in transplantation therapy. Conophylline may thus be useful for the large-scale preparation of porcine insulin-producing cells for the regeneration therapy of type-1 diabetes mellitus.