IL-1 resets glucose homeostasis at central levels.

Abstract

Administration of IL-1beta 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-1beta 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-1beta 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.

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@article{Rey2006IL1RG, title={IL-1 resets glucose homeostasis at central levels.}, author={Adriana del Rey and Eduardo Angel Roggero and Anke Randolf and Carolina V Mahuad and S M Mccann and Val{\'e}ria Rettori and Hugo Oscar Besedovsky}, journal={Proceedings of the National Academy of Sciences of the United States of America}, year={2006}, volume={103 43}, pages={16039-44} }