Interleukin‐1β and Insulin Elicit Different Neuroendocrine Responses to Hypoglycemia

Abstract

Interleukin (IL)-1beta induces a prolonged hypoglycemia in mice that is not caused by a reduction in food intake and is dissociable from insulin effects. There is a peripheral component in the hypoglycemia that the cytokine induces resulting from an increased glucose uptake, an effect that can be exerted in a paracrine fashion at the site where IL-1 is locally produced. However, the maintenance of hypoglycemia is controlled at brain levels because the blockade of IL-1 receptors in the central nervous system inhibits this effect to a large extent. Furthermore, there is evidence that the cytokine interferes with counter regulation to hypoglycemia. Here we report that administration of IL-1 or long-lasting insulin results in different changes in food intake and in neuroendocrine mechanisms 8 h following induction of the same degree of hypoglycemia (40-45% decrease in glucose blood levels). Insulin, but not IL-1, caused an increase in food intake and an endocrine response that tends to reestablish euglycemia. Conversely, a decrease in noradrenergic and an increase in serotonergic activity in the hypothalamus occur in parallel with a reduction of glucose blood levels only in IL-1-treated mice, effects that can contribute to the maintenance of hypoglycemia. These results are compatible with the proposal that IL-1 acting in the brain can reset glucose homeostasis at a lower level. The biologic significance of this effect is discussed.

A Multifaceted Analysis of Immune-Endocrine-Metabolic Alterations in Patients with Pulmonary Tuberculosis

“…This cytokine was not only increased during TB but also negatively correlated with the BMI. At the experimental level IL-1β is known to produce a profound hypoglycemia in mice and a re-setting of glucose homeostasis that favors fuel re-distribution towards immune cells but with a paradoxical reduction of food intake [33]. Moreover leptin actions on food intake and body temperature appear to be mediated by IL-1 [34].…”

Inflammation during obesity is not all bad: evidence from animal and human studies

“…IL-1 modulates glucose homeostasis by impairing insulin signaling, modulating insulin secretion, augmenting insulinindependent glucose uptake, increasing energy expenditure, and stimulating autonomic nervous system activity (58,70,97,107). Depending on the dose, IL-1 can induce hypoglycemia or hyperglycemia (70,138).…”

<p>Hypoglycemia After Upper Gastrointestinal Surgery: Clinical Approach to Assessment, Diagnosis, and Treatment</p>

“…32 IL-1β also decreases the threshold for noradrenergic response in the hypothalamus (where IL-1B is expressed). 33,34 Treatment of individuals with PBH with an Il-1B antagonist increased nadir glucose during meal testing. 35 Whether aberrant inflammatory responses contribute more broadly to PBH will require additional study.…”