Effect of bacterial sepsis on gluconeogenic capacity in the rat.
Since sepsis places increased demands on the host for energy and on other substrates for tissue repair and host defense, hepatic gluconeogenesis is critical for the host's adaptation to sepsis. Substrate-stimulated gluconeogenesis (i.e., gluconeogenic capacity) was assessed by the alanine load method in mannoheptulose-pretreated rats made septic by cecal ligation after laparotomy, as well as by cecal ligation and puncture after laparotomy. Fasted rats subjected to laparotomy only (sham-ligated) and fasted, nonoperated rats (controls) were investigated simultaneously. Following an overnight (-18 to 0 hr) fast, nonoperated animals converted 17.9 +/- 1.5% of [14C]alanine to [14C]glucose. Continued fasting in nonoperated animals resulted in enhanced (P less than 0.05) gluconeogenic capacity (6 hr = 27.2 +/- 3.0%; 24 hr = 26.2 +/- 1.9%; and 48 hr = 28.5 +/- 2.6%) relative to Time 0. Laparotomy alone (sham ligation) delayed the fasting-induced increase (P less than 0.05) in gluconeogenesis capacity (6 hr = 21.1 +/- 1.2%; 24 hr = 18.5 +/- 1.3%; 48 hr = 27.8 +/- 1.0%) relative to Time 0. In contrast, postoperative sepsis produced a sustained depression (P less than 0.05) of gluconeogenic capacity relative to nonoperated sham-ligated controls at 48 hr (cecal ligation, 18.4 +/- 1.4%; and cecal ligation and puncture, 18.8 +/- 1.2%). Thus, (1) fasting enhances hepatic gluconeogenic capacity; (2) surgical trauma transiently blunts the gluconeogenic response to fasting; and (3) sepsis undermines the gluconeogenic response to fasting.
D000409:Alanine / Q000008:administration & dosage / Q000378:metabolism; D000818:Animals; D001424:Bacterial Infections / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis; D002250:Carbon Radioisotopes; D002432:Cecum / Q000601:surgery; D005215:Fasting; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood; D007813:Laparotomy; D008026:Ligation; D008099:Liver / Q000378:metabolism*; D008297:Male; D011677:Punctures; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007328:Insulin; D005947:Glucose; D000409:Alanine