Cornell R P
Am J Physiol. 1981 Dec;241(6):E428-35. doi: 10.1152/ajpendo.1981.241.6.E428.
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.
在通过部分（67%）肝切除术、四氯化碳灌胃和静脉注射D-半乳糖胺造成实验性肝损伤24小时后的禁食大鼠中，出现了基础门静脉和全身静脉高胰岛素血症及高胰高血糖素血症。胰腺激素分泌增强和肝脏激素摄取减少都可能是胰岛素和胰高血糖素供应过多的原因。内源性肠道来源的内毒素被认为是激素反应过度的致病因素，因为静脉注射外源性内毒素会引起相同程度的胰岛素和胰高血糖素升高。肝损伤后24小时的全身内毒素血症通过铅致敏大鼠的显著（78 - 100%）致死率以及血浆样本的鲎试剂凝胶化试验呈阳性得以表明。此外，抗内毒素治疗，包括内毒素耐受、多粘菌素B和肠道除菌，在大多数肝损伤组中显著降低了24小时时的铅致敏致死率以及高胰岛素血症和高胰高血糖素血症反应。低剂量内毒素门静脉与全身静脉给药的对比表明，肝脏对正常内毒素的吞噬作用抑制了胰腺内分泌反应。假设存在一种生理负反馈控制系统，即肝损伤后肠道来源的全身内毒素血症，胰腺分泌过多的胰岛素和胰高血糖素以刺激肝脏再生。
