AJP - Endocrinology and Metabolism, Vol 241, Issue 6 428-E435, Copyright © 1981 by American Physiological Society

ARTICLES

Endotoxin-induced hyperinsulinemia and hyperglucagonemia after experimental liver injury

R. P. Cornell

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.

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