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.
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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)
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Copyright | Copyright (c) 2009 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- Biomarkers
- Insulin
- Vinca Alkaloids
- conophylline
- Niacinamide
- Glucose
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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)
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