Alterations of G-protein and adenylate cyclase signaling in rat liver during the progression of sepsis

Changes in the protein level of various subunits of G-protein and the activ ity of adenylate cyclase in rat liver plasma membranes during different met abolic phases of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). The results show that the protein levels of G alpha i-2 and G alpha i-3 were unchanged during the early hypermetabolic (hyperglyce mic) phase (9 h after CLP), whereas G alpha ai-2 and G alpha ai3 were incre ased by 32.4 and 59.1%, respectively, during the late hypometabolic (hypogl ycemic) phase (18 h after CLP) of sepsis. The protein levels of G alpha s a nd G beta remained unaltered during both the early and the late phases of s epsis. The activity of adenylate cyclase remained unchanged during the earl y phase, whereas it was decreased by 26% (p < .05) during the late phase of sepsis. Since the G-protein/adenylate cyclase signaling system mediates ho rmonal control of hepatic glucose metabolism, the observed increases in the G alpha i-2 and G alpha i-3 protein levels coupled with a decrease in the activity of adenylate cyclase may contribute to the development of the hypo glycemia during the late stage of sepsis.