title: Endotoxin-induced hyperinsulinemia and hyperglucagonemia after experimental liver injury.
abstract: Basal portal and systemic venous hyperinsulinemia and hyperglucagonemia were present in fasted rats at 24 h after experimental liver injury by partial (67%) hepatectomy, carbon tetrachloride gavage, and intravenous D-galactosamine administration. Both enhanced pancreatic hormone secretion and depressed hepatic hormone extraction were likely responsible for the insulin and glucagon oversupply. Endogenous gut-derived endotoxin is proposed as the causative factor for the exaggerated hormonal response because intravenous exogenous endotoxin elicited an identical elevation of insulin and glucagon. Systemic endotoxemia at 24 h after liver injury was indicated by marked (78-100%) lethality in lead-sensitized rats and positive Limulus lysate gelation tests of plasma samples. Furthermore, antiendotoxin treatments, including endotoxin tolerance, polymyxin B, and gut sterilization, significantly reduced both lead-sensitized lethality and hyperinsulinemic and hyperglucagonemic responses at 24 h in most liver-injury groups. Portal versus systemic venous administration of endotoxin at a low dose implied that normal endotoxin phagocytosis by the liver suppressed the pancreatic endocrine response. A physiological negative-feedback control system involving gut-derived systemic endotoxemia after liver damage with insulin and glucagon hypersecretion by the pancreas for stimulation of hepatic regeneration is hypothesized.
mesh_terms: D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000097:blood; D004195:Disease Models, Animal; D004731:Endotoxins / Q000097:blood*; D005688:Galactosamine / Q000633:toxicity; D005934:Glucagon / Q000097:blood*; D006498:Hepatectomy; D006946:Hyperinsulinism / Q000209:etiology*; D008107:Liver Diseases / Q000097:blood* / Q000150:complications; D008297:Male; D051381:Rats; D012477:Salmonella enteritidis
chemical_list: D004731:Endotoxins; D005688:Galactosamine; D005934:Glucagon