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

Abstract

We previously found that conophylline, an alkaloid isolated from the leaves of Ervatamia microphylla, induced beta-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 beta-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.

• Authors: M Kawakami, A Hirayama, K Tsuchiya, H Ohgawara, M Nakamura, K Umezawa
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 64 Issue 3 Pg. 226-31 (Mar 2010) ISSN: 1950-6007 [Electronic] France
• PMID: 20079600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

Chemical References

• Biomarkers
• Insulin
• Vinca Alkaloids
• conophylline
• Niacinamide
• Glucose

Topics

• Animals
• Animals, Newborn
• Biomarkers
• Cell Differentiation (drug effects)
• Cells, Cultured (drug effects)
• Drug Evaluation, Preclinical
• Drug Synergism
• Gene Expression Regulation (drug effects)
• Glucose (pharmacology)
• Insulin (metabolism)
• Insulin Secretion
• Islets of Langerhans (drug effects, metabolism)
• Molecular Structure
• Niacinamide (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Sus scrofa
• Swine
• Vinca Alkaloids (chemistry, pharmacology)