Interleukin-1beta and insulin elicit different neuroendocrine responses to hypoglycemia.
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.
Ota
Kazuki
K
Department of Immunophysiology, Institute of Physiology and Pathophysiology, Medical Faculty, Philipps University, Marburg, Germany.
Wildmann
Johannes
J
Ota
Taeko
T
Besedovsky
Hugo O
HO
Del Rey
Adriana
A
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004837:Epinephrine / Q000097:blood; D005247:Feeding Behavior / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D053583:Interleukin-1beta; D018377:Neurotransmitter Agents; D003345:Corticosterone; D009638:Norepinephrine; D004837:Epinephrine