CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
artículos
Título:
IL-1 resets glucose homeostasis at central levels
Autor/es:
ADRIANA DEL REY; EDUARDO ROGGERO; ANKE RANDOLF; CAROLINA MAHUAD; SAMUEL MCCANN; VALERIA BESUHLI DE RETTORI; HUGO O. BESEDOVSKY
Revista:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Referencias:
Año: 2006 vol. 103 p. 16039 - 16044
ISSN:
0027-8424
Resumen:
Administration of IL-1 results in a profound and long-lasting
hypoglycemia. Here, we show that this effect can be elicited by
endogenous IL-1 and is related to not only the capacity of the
cytokine to increase glucose uptake in peripheral tissues but also
to mechanisms integrated in the brain. We show that (i) blockade
of IL-1 receptors in the brain partially counteracted IL-1-induced
hypoglycemia; (ii) peripheral administration or induction of IL-1
production resulted in IL-1 gene expression in the hypothalamus
of normal and insulin-resistant, leptin receptor-deficient, diabetic
db_db mice; (iii) IL-1 treated normal and db_db mice challenged
with glucose did not return to their initial glucose levels but
remained hypoglycemic for several hours. This effect was largely
antagonized by blockade of IL-1 receptors in the brain; and (iv)
when animals with an advanced Type II diabetes were treated with
IL-1 and challenged with glucose, they died in hypoglycemia.
However, when IL-1 receptors in the brains of these diabetic mice
were blocked, they survived, and glucose blood levels approached
those that these mice had before IL-1 administration. The prolonged
hypoglycemic effect of IL-1 is insulin-independent and
develops against increased levels of glucocorticoids, catecholamines,
and glucagon. These findings, together with the present
demonstration that this effect is integrated in the brain and is
paralleled by IL-1 expression in the hypothalamus, indicate that
this cytokine can reset glucose homeostasis at central levels. Such
reset, along with the peripheral actions of the cytokine, would
favor glucose uptake by immune cells during inflammatory
immune processes.