Hepatic microvascular regulatory mechanisms. VIII. Glucogenic responses and morphologic changes following serotonin-induced low flow.
Changes in blood glucose, hepatic glycogen content and distribution, the number of hepatic mast cells, and hepatic morphology were assessed over 30 min in non-fasted and anesthetized Sprague-Dawley rats receiving endoportal or femoral intravenous injections of selected doses of serotonin and/or phentolamine, lodoxamide, or of Ringer's solution (control). Endoportal administration of low-flow producing doses of serotonin (1.0, 10.0, 20.0 micrograms per 100 g b.w.) elevated circulating blood glucose without decreasing hepatic glycogen content when compared to control in unit dry or wet weights. Hyperglycemia was accompanied by centrilobular glycogen depletion and apparent Kupffer cell activation. However, no change in hepatocyte or endothelial cell morphology or in the number of hepatic mast cells was observed following serotonin-induced low flow. The glucotropic response to a nonhypotensive dose of serotonin (1.0 microgram per 100 g b.w.) was modified by phentolamine (100 micrograms per 100 g b.w.) but not lodoxamide (0.1 microgram per 100 g b.w.). These blockers, when given alone, stimulated centrilobular glycogen depletion without producing a net change in blood glucose or hepatic glycogen content. By contrast, injection of serotonin (10.0 micrograms per 100 g b.w.) and/or phentolamine (100 micrograms per 100 g b.w.) into the femoral vein provoked no glucogenesis or systemic hypotension. Given these results, serotonin is suggested to stimulate hyperglycemia by activating alpha-adrenergic receptors. Since centrilobular glycogen depletion proceeds with no detectable change in total hepatic glycogen content, it is postulated that hepatic glycogen catabolism and deposition occur simultaneously and at equivalent rates during conditions of serotonin-induced hyperglycemia and low flow.
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000648:ultrastructure; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000648:ultrastructure; D008833:Microcirculation / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*
D001786:Blood Glucose; D008112:Liver Glycogen; D012701:Serotonin