Central interleukin 1-elicited hyperinsulinemia is mediated by prostaglandins but not autonomics.
This laboratory previously reported that centrally administered interleukin 1 (IL-1) in fasted pentobarbital-anesthetized rats elicited significant hyperinsulinemic and febrile responses. In characterizing this putative central mechanism for the regulation of pancreatic insulin secretion, hyperinsulinemia and fever elicited by IL-1 injected intravenously (iv) or intracerebroventricularly (icv) was totally eliminated by prior cyclooxygenase inhibition with indomethacin, ibuprofen, or meclofenamate but not lipoxygenase inhibition with propyl gallate or leukotriene receptor antagonism with LY 171883. Furthermore, central administration of prostaglandin E2 at 10 and 100 ng doses consistently evoked hyperinsulinemic, hypercorticotropinemic, and febrile responses in anesthetized rats maintained on isothermal pads. beta-Adrenergic and vagus nerves to the pancreatic beta-cells seemed likely candidates to mediate the enhanced secretion of insulin elicited by IL-1 acting centrally. However, pretreatment of rats with hexamethonium, propanolol, atropine, or bilateral subdiaphragmatic vagotomy all failed to reduce hyperinsulinemia after IL-1 iv or icv. This evidence suggests that the central mechanism for enhanced pancreatic insulin secretion elicited by IL-1 may depend on a humoral rather than autonomic neural efferent pathway. Moreover, the hyperinsulinemia is mediated in part by prostaglandins just like the well-studied febrile response.
Cornell
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RP
Division of Science, Northeast Missouri State University, Kirksville 63501.
D000098:Acetophenones / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D001831:Body Temperature / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology*; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006946:Hyperinsulinism / Q000139:chemically induced*; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007276:Injections, Intraventricular; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011435:Propyl Gallate / Q000494:pharmacology; D051381:Rats; D012016:Reference Values; D013189:SRS-A / Q000037:antagonists & inhibitors; D013777:Tetrazoles / Q000494:pharmacology; D014628:Vagotomy
D000098:Acetophenones; D006584:Hexamethonium Compounds; D007328:Insulin; D007375:Interleukin-1; D013189:SRS-A; D013777:Tetrazoles; D018738:Hexamethonium; D008469:Meclofenamic Acid; D001285:Atropine; C044660:LY 171883; D011435:Propyl Gallate; D000324:Adrenocorticotropic Hormone; D005934:Glucagon; D011433:Propranolol; D015232:Dinoprostone; D007052:Ibuprofen; D007213:Indomethacin; D010646:Phentolamine