Altered Ca2+ homeostasis and functional correlates in hepatocytes and adipocytes in endotoxemia and sepsis.
Decreased cytosolic [Ca2+] and impaired Ca2+ release in response to an IP3 challenge are among perturbations in hepatocyte Ca2+ homeostasis associated with endotoxemia and sepsis. These changes are consistent with the accompanying alterations in appropriate physiologic functions, e.g., activation of glycogen phosphorylase and gluconeogenesis, mediated by [Ca2+]c and defective phosphorylation of relevant enzymes. Attenuation of IP3 binding to the subcellular fractions that are imputed to be targets of IP3 and a decrease in the size of the IP3-sensitive pool of releasable Ca2+ are underlying components of the mechanism of the reduced Ca2+ release upon IP3 stimulation and its metabolic sequelae. ET treatment leads to a significant increase in Ca2+ associated with the cell surface compartment of adipocytes, a reduction in 45Ca2+ uptake by endoplasmic reticulum and higher cytosolic [Ca2+] under basal conditions and upon ACTH stimulation than that observed in cells of control rats. The reduced 45Ca2+ uptake is also manifest in adipocytes of septic rats. Alterations in adipocyte metabolism induced by ET include increased oxidation of glucose to CO2 (an insulin-like effect) and increased lipolysis upon NE and ACTH stimulation.
Spitzer
J A
JA
Department of Physiology, LSU Medical Center, New Orleans 70112.
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000378:metabolism*; D006706:Homeostasis; D007293:Inosine Triphosphate / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D006005:Phosphorylases / Q000378:metabolism; D014115:Toxemia / Q000378:metabolism*
D007293:Inosine Triphosphate; D006005:Phosphorylases; D002118:Calcium