High Glucose Stimulates Early Response Gene c-Myc Expression in Rat Pancreatic β Cells

Jean-Christophe Jonas, D. Ross Laybutt, Garry M. Steil, Nitin Trivedi, José G. Pertusa, Mark Van de Casteele, Gordon C. Weir, Jean-Claude Henquin
2001 Journal of Biological Chemistry  
Glucose-induced insulin secretion from hyperglycemic 90% pancreatectomized rats is markedly impaired, possibly because of loss of ␤ cell differentiation. Association of these changes with ␤ cell hypertrophy, increased mRNA levels of the transcription factor c-Myc, and their complete normalization by phlorizin treatment suggested a link between chronic hyperglycemia, increased c-Myc expression, and altered ␤ cell function. In this study, we tested the effect of hyperglycemia on rat pancreatic
more » ... et c-Myc expression both in vivo and in vitro. Elevation of plasma glucose for 1-4 days (glucose infusion/clamp) was followed by parallel increases in islet mRNA levels (relative to TATA-binding protein) of c-Myc and two of its target genes, ornithine decarboxylase and lactate dehydrogenase A. Similar changes were observed in vitro upon stimulation of cultured islets or purified ␤ cells with 20 and 30 mmol⅐liter ؊1 glucose for 18 h. These effects of high glucose were reproduced by high potassium-induced depolarization or dibutyryl-cAMP and were inhibited by agents decreasing cytosolic Ca 2؉ or cAMP concentrations. In conclusion, the expression of the early response gene c-Myc in rat pancreatic ␤ cells is stimulated by high glucose in a Ca 2؉ -dependent manner and by cAMP. c-Myc could therefore participate to the regulation of ␤ cell growth, apoptosis, and differentiation under physiological or pathophysiological conditions.
doi:10.1074/jbc.m105020200 pmid:11457846 fatcat:on4ruit3tzaydnj2vzjtmpdwim