Altered control of carbohydrate metabolism in endotoxemia.

J. J. Spitzer, G. J. Bagby, K. Meszaros, C. H. Lang

Research output: Contribution to journalReview article

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Abstract

Based on our data, we envisage the following sequence of events to occur after the administration of a moderately severe dose of endotoxin: Sympathetic stimulation due to hypotension, and possibly other factors, increases plasma concentration of catecholamines. Increased hepatic phosphorylase a activity depletes existing glycogen stores and causes transient hyperglycemia. Lactate release from skeletal muscle is also enhanced, due to the more sustained activation of muscle phosphorylase a and increased uptake of plasma glucose. Stimulation of the immunologically active tissues by endotoxin with the participation of mononuclear phagocytes and TNF results in elevated glycolysis in these tissues as well, thus further enhancing the hyperlactacidemia. The increased precursor concentration and their delivery to the liver stimulate gluconeogenesis, in spite of endotoxin-induced suppression of PEPCK activity. Thus, an elevated precursor supply accelerates gluconeogenesis which is primarily responsible for the increased glucose Ra when hepatic glycogen stores are depleted. It appears that both an increase in blood lactate and catecholamines are important in maintaining the increased gluconeogenesis. This is illustrated schematically in Fig. 4. We postulate that in the fasted nutritionally nonsupported rat, endotoxin enhances glucose utilization in immunologically active tissues as well as in muscle. The presence of catecholamines and the glycolytically produced lactate stimulates gluconeogenesis. These events support the mounting of an effective immune response and aid the body to maintain the immune response by conserving glucose carbon.

Original languageEnglish (US)
Pages (from-to)145-165
Number of pages21
JournalProgress in Clinical and Biological Research
Volume286
StatePublished - Jan 1 1989

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All Science Journal Classification (ASJC) codes

  • Medicine(all)

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