TY - JOUR
T1 - Role of IL-1α in central nervous system immunomodulation of glucoregulation
AU - Lang, Charles H.
AU - Molina, Patricia E.
AU - Yousef, Khalil A.
AU - Tepper, Patrick G.
AU - Abumrad, Naji N.
N1 - Funding Information:
Acknowledgements. Recombinant human IL-1/3 was generously provided by the Biological Resources Branch of the Biological Response Modifiers Program, Division of Cancer Treatment/NCl. IL-la was generously provided by Hoffman-LaRoche, Nutley, NJ. The authors would also like to thank Ms. Gale Forrester, Dawn Sasvary and Joanne Moeller for their expert technical assistance. This work was supported by National Institute of General Medical Science Grants GM 38032 and RR05736 (BRSG to SUNY-Stony Brook).
PY - 1993/10/8
Y1 - 1993/10/8
N2 - Hyperglycemia is a hallmark of the stress response, and has been largely attributed to elevated plasma levels of catabolic hormones. Recently, various cytokines have been shown to be endogenously produced within the brain and may represent an important component of the central regulation of this metabolic response. Therefore, the aim of the present study was to determine whether the intracerebroventricular (i.c.v.) injection of one such peptide, interleukin (IL)-1, can produce hormonal and metabolic alterations comparable to those observed under stress conditions. An i.c.v. cannula and vascular catheters were placed in rats prior to the experiment. Whole body glucose flux was assessed in overnight fasted conscious unrestrained rats using [3-3H]glucose. A mild hyperglycemia was elicited 20 min after the i.c.v. injection of IL-1α (human recombinant, 100 ng) that was not detected in control rats. Glucose levels gradually increased and were 26% higher than control values during the last hour of the 3 h experimental period. The hyperglycemia resulted from a 44% increase in the rate of hepatic glucose output (HGO), which preceded a propertional rise in peripheral glucose utilization. No increase in metabolic clearance rate was observed, suggesting that the increased glucose uptake was the result of mass action. The increased glucose flux was associated with a transient hyperinsulinemia (+95%), and sustained elevations in the arterial concentrations of glucagon (56%) and corticosterone (175%). In contrast, glucose flux was not altered by intravenous administration of the same dose of IL-1α, or i.c.v. injection of IL-1β, or heat-inactivated IL-1α. Indomethacin (5 mg/kg, i.v.) blocked the hyperglycemia and increased HGO induced by i.c.v. injection of prostaglandin E2 (100 ng) produced comparable increases in glucose flux. These results indicate that IL-1α can act centrally to enhance whole body glucose metabolism, and that this response is probably mediated by prostaglandins.
AB - Hyperglycemia is a hallmark of the stress response, and has been largely attributed to elevated plasma levels of catabolic hormones. Recently, various cytokines have been shown to be endogenously produced within the brain and may represent an important component of the central regulation of this metabolic response. Therefore, the aim of the present study was to determine whether the intracerebroventricular (i.c.v.) injection of one such peptide, interleukin (IL)-1, can produce hormonal and metabolic alterations comparable to those observed under stress conditions. An i.c.v. cannula and vascular catheters were placed in rats prior to the experiment. Whole body glucose flux was assessed in overnight fasted conscious unrestrained rats using [3-3H]glucose. A mild hyperglycemia was elicited 20 min after the i.c.v. injection of IL-1α (human recombinant, 100 ng) that was not detected in control rats. Glucose levels gradually increased and were 26% higher than control values during the last hour of the 3 h experimental period. The hyperglycemia resulted from a 44% increase in the rate of hepatic glucose output (HGO), which preceded a propertional rise in peripheral glucose utilization. No increase in metabolic clearance rate was observed, suggesting that the increased glucose uptake was the result of mass action. The increased glucose flux was associated with a transient hyperinsulinemia (+95%), and sustained elevations in the arterial concentrations of glucagon (56%) and corticosterone (175%). In contrast, glucose flux was not altered by intravenous administration of the same dose of IL-1α, or i.c.v. injection of IL-1β, or heat-inactivated IL-1α. Indomethacin (5 mg/kg, i.v.) blocked the hyperglycemia and increased HGO induced by i.c.v. injection of prostaglandin E2 (100 ng) produced comparable increases in glucose flux. These results indicate that IL-1α can act centrally to enhance whole body glucose metabolism, and that this response is probably mediated by prostaglandins.
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U2 - 10.1016/0006-8993(93)90059-V
DO - 10.1016/0006-8993(93)90059-V
M3 - Article
C2 - 8252416
AN - SCOPUS:0027317718
SN - 0006-8993
VL - 624
SP - 53
EP - 60
JO - Brain research
JF - Brain research
IS - 1-2
ER -