Alterations in hepatic membrane potentials in vivo during early and late sepsis

To determine whether alterations in hepatocyte membrane electrical responses might play a role in glucose dyshomeostasis during sepsis, hepatocyte membrane potentials were measured in vivo in rats made septic by cecal ligation and puncture (CLP). In both early-septic (8-10 hr after CLP) and late-septic (18-20 hr after CLP) rats, resting hepatocyte membrane potentials were significantly depressed compared to those in sham-operated rats. In addition, the hyperpolarization response to glucagon administration in vivo which was observed in the sham-operated rats was significantly attenuated in both early- and late-sepsis rats. To determine whether this blunted hyperpolarization response was related to defects in stimulation of gluconeogenesis, livers from sham-operated and early-sepsis rats were isolated and perfused. The livers from sham-operated rats responded to 1 nM glucagon by increasing glucose release by 53%, while those from septic rats increased by only 20%. These results suggest that a defect associated with the plasma membrane may be an early event in the development of glucose dyshomeostasis during sepsis.