Reduced hepatic blood flow does not limit gluconeogenesis in awake endotoxic minipigs

Hypoglycemia associated with endotoxic shock is due to increased glucose utilization coupled with inadequate hepatic glucogenesis. Decreased hepatic blood flow is common in shock and could conceivably reduce hepatic gluconeogenic substrate and oxygen delivery, thereby limiting gluconeogenesis. A study was conducted to assess endotoxin-induced alteration of hepatic hemodynamics and its effect on glucose metabolism. Eight adult minipigs were fitted with jugular, portal, and hepatic vein and carotid artery catheters, and hepatic artery and portal vein flow cuffs for determination of transhepatic kinetics. Three days later they were infused with endotoxin at 15 micrograms/kg/hr. Hepatic blood flow and portal vein oxygen (O2) content became significantly (P less than or equal to 0.05) reduced thereby decreasing hepatic O2 input. Hepatic O2 extraction increased from 24 to 73% but never achieved the reported maximum of 97%. Therefore, reduction of O2 input did not seem to rate limit gluconeogenesis. Reductions in gluconeogenic substrate delivery were not involved since hepatic lactate and pyruvate input actually increased due to elevated blood lactate and pyruvate concentrations.