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Abstract
Hypothesizing that UCP2 may influence insulin
secretion by modifying the ATP/ADP ratio within
pancreatic islets, we have investigated the expression
of intraislet UCP2 gene in rats showing insulin
oversecretion (non-diabetic Zucker fa/fa obese rats,
glucose-infused Wistar rats) or insulin undersecretion
(fasting and mildly diabetic rats). We found that
in Zucker fa/fa obese rats, hyperinsulinemia
(1222 ± 98 pmol/1 vs. 128 ± 22 pmol/1 in lean Zucker
rats) was accompanied by a significant increase in
UCP2 mRNA levels. In rat submitted to a 5 day
infusion with glucose, hyperinsulinemia (1126 ± 101
pmol/l vs. 215 ± 25 pmol/1 in Wistar control rats),
coincided with an enhanced intraislet UCP2 gene
expression, whereas a 8h or a 2 day-infusion did not
induce significant changes in UCP2 mRNA expression.
In rats made hypoinsulinemic and mildly
diabetic by the injection of a low dose of streptozotocin,
and in 4-day-fasting rats (plasma insulin
28 ± 5 pmol/1) UCP2 gene expression was sharply
decreased. A 3-day-fast was ineffective. The data
show the existence of a time-dependent correlation
between islet mRNA UCP2 and insulin that may be
interpreted as an adaptative response to prolonged
insulin excess.