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J. Biol. Chem., Vol. 276, Issue 38, 35375-35381, September 21, 2001
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From the Glucose-induced insulin secretion from
hyperglycemic 90% pancreatectomized rats is markedly impaired,
possibly because of loss of
High Glucose Stimulates Early Response Gene c-Myc Expression in
Rat Pancreatic
Cells*
§,,
**,
Unit of Endocrinology and Metabolism,
University of Louvain, Brussels, Belgium, the ¶ Section of Islet
Transplantation and Cell Biology, Joslin Diabetes Center, Boston,
Massachusetts, and the Diabetes Research Center, Vrije
Universiteit Brussels, Brussels, Belgium
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 islet
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 mmol·liter
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 Ca2+ 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
Ca2+-dependent manner and by cAMP. c-Myc could
therefore participate to the regulation of cell growth, apoptosis,
and differentiation under physiological or pathophysiological conditions.
*
This work was supported by Grants 1.5.133.00 and 3.4552.98 from the Fonds National de la Recherche Scientifique (Brussels), funds
from the Interuniversity Poles of Attraction Program (P4/21)-Belgian State, Grant 00/05-260 from the General Direction of Scientific Research of the French Community of Belgium, and National Institutes of
Health Grant DK-35449 (to G. C. W.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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