Diabetes, Vol 37, Issue 10 1405-1410, Copyright © 1988 by American Diabetes Association

ARTICLES

Sodium butyrate increases glucagon and insulin gene expression by recruiting immunocytochemically negative cells to produce hormone

AC Powers, J Philippe, H Hermann and JF Habener
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston 02114.

Current evidence suggests that a multipotential endodermal progenitor cell may give rise to all islet cell phenotypes. We characterized two hormone-producing rat islet (RIN) cell lines derived from a radiation-induced islet tumor by immunocytochemistry, Northern blot analysis, and radioimmunoassay of secreted hormone. Using antisera to glucagon, insulin, and somatostatin, we found that less than 15% of the cells in any of these three islet cell lines contained immunopositive cells. The number of cells staining for the hormone correlated with mRNA levels and immunoreactive secreted hormones. Sodium butyrate, a short-chain aliphatic fatty acid, slowed cell growth and increased dramatically the percentage of cells staining for glucagon and insulin. The increase in immunopositive cells was accompanied by an increase in glucagon and insulin mRNAs and secreted glucagon and insulin. These observations indicate that sodium butyrate increases glucagon and insulin gene expression by recruiting previously immunonegative cells to produce hormone. The relationship of DNA synthesis and hormone production was assessed by pulse-labeling RIN cells with [3H]thymidine, which was followed by autoradiography and immunocytochemistry. [3H]thymidine incorporation was observed in a lower percentage of immunopositive compared with immunonegative cells. Furthermore, sodium butyrate reduced the number of [3H]thymidine-labeled cells and increased the number of immunopositive cells. These observations suggest that sodium butyrate differentiates the islet cells and thereby increases the expression of the glucagon and insulin genes.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. M. Rukstalis, M. Ubeda, M. V. Johnson, and J. F. Habener Transcription Factor Snail Modulates Hormone Expression in Established Endocrine Pancreatic Cell Lines Endocrinology, June 1, 2006; 147(6): 2997 - 3006. [Abstract] [Full Text] [PDF]

				J. F. List and J. F. Habener Glucagon-like peptide 1 agonists and the development and growth of pancreatic {beta}-cells Am J Physiol Endocrinol Metab, June 1, 2004; 286(6): E875 - E881. [Abstract] [Full Text] [PDF]

				X. Cao, G. Flock, C. Choi, D. M. Irwin, and D. J. Drucker Aberrant Regulation of Human Intestinal Proglucagon Gene Expression in the NCI-H716 Cell Line Endocrinology, May 1, 2003; 144(5): 2025 - 2033. [Abstract] [Full Text] [PDF]

				G. Cabrera-Valladares, M. S. German, F. M. Matschinsky, J. Wang, and C. Fernandez-Mejia Effect of Retinoic Acid on Glucokinase Activity and Gene Expression and on Insulin Secretion in Primary Cultures of Pancreatic Islets Endocrinology, July 1, 1999; 140(7): 3091 - 3096. [Abstract] [Full Text]