Tumor necrosis factor enhances glucose uptake by peripheral tissues

D. A. Evans, D. O. Jacobs, D. W. Wilmore

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Anesthetized dogs received a constant intravenous infusion of tumor necrosis factor (TNF) or saline over 6 h. Glucose kinetics were studied by determining the rate of glucose turnover and hindlimb substrate flux. Cardiovascular responses were monitored and concentrations of counterregulatory hormones were also measured. TNF infusion caused a fall in blood glucose concentration from 4.6 ± 0.1 to 3.9 ± 0.2 mmol/l by 6 h (P < 0.05). This mild hypoglycemia was associated with increased circulating levels of cortisol, glucagon, and epinephrine. The rate of glucose production increased from 26.5 ± 2.1 to 32.5 ± 0.7 μmol · min-1 · kg body wt-1 (P < 0.05) over the 6-h infusion period; this response was associated with increased glucose disappearance (26.4 ± 2.2 to 32.7 ± 0.9 μmol · min-1 · kg body wt-1, P < 0.05) and enhanced clearance (5.7 ± 0.5 to 9.0 ± 0.6 ml · min-1 · kg body wt-1, P < 0.05). As blood glucose levels fell, hindlimb glucose uptake and glucose clearance increased markedly in TNF-infused animals as compared with controls despite a 50% fall in mean serum insulin concentration. The exchange of lactate, pyruvate, and total amino acid nitrogen across the hindlimbs was similar in both groups of animals. However, arterial concentrations of lactate and pyruvate rose to two to three times their initial values. The hypoglycemia associated with the infusion of TNF results from a disparity between the rate of glucose appearance and disappearance. There is an increased uptake of glucose across the hindlimb; this response appears to be independent of insulin concentrations and may be related to direct effects of TNF. Pyruvate and lactate concentrations rise because of altered central clearance and/or increased production in visceral tissues.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume257
Issue number5
StatePublished - 1989
Externally publishedYes

Fingerprint

Tumor Necrosis Factor-alpha
Glucose
Hindlimb
Pyruvic Acid
Lactic Acid
Hypoglycemia
Blood Glucose
Insulin
Glucagon
Intravenous Infusions
Epinephrine
Hydrocortisone
Nitrogen
Hormones
Dogs
Amino Acids
Serum

Keywords

  • glucose kinetics
  • glucose metabolism in hindlimb
  • tumor necrosis factor infusion

ASJC Scopus subject areas

  • Physiology

Cite this

Tumor necrosis factor enhances glucose uptake by peripheral tissues. / Evans, D. A.; Jacobs, D. O.; Wilmore, D. W.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 257, No. 5, 1989.

Research output: Contribution to journalArticle

@article{fd4982fea8b948dfb9d94cd3febdab35,
title = "Tumor necrosis factor enhances glucose uptake by peripheral tissues",
abstract = "Anesthetized dogs received a constant intravenous infusion of tumor necrosis factor (TNF) or saline over 6 h. Glucose kinetics were studied by determining the rate of glucose turnover and hindlimb substrate flux. Cardiovascular responses were monitored and concentrations of counterregulatory hormones were also measured. TNF infusion caused a fall in blood glucose concentration from 4.6 ± 0.1 to 3.9 ± 0.2 mmol/l by 6 h (P < 0.05). This mild hypoglycemia was associated with increased circulating levels of cortisol, glucagon, and epinephrine. The rate of glucose production increased from 26.5 ± 2.1 to 32.5 ± 0.7 μmol · min-1 · kg body wt-1 (P < 0.05) over the 6-h infusion period; this response was associated with increased glucose disappearance (26.4 ± 2.2 to 32.7 ± 0.9 μmol · min-1 · kg body wt-1, P < 0.05) and enhanced clearance (5.7 ± 0.5 to 9.0 ± 0.6 ml · min-1 · kg body wt-1, P < 0.05). As blood glucose levels fell, hindlimb glucose uptake and glucose clearance increased markedly in TNF-infused animals as compared with controls despite a 50{\%} fall in mean serum insulin concentration. The exchange of lactate, pyruvate, and total amino acid nitrogen across the hindlimbs was similar in both groups of animals. However, arterial concentrations of lactate and pyruvate rose to two to three times their initial values. The hypoglycemia associated with the infusion of TNF results from a disparity between the rate of glucose appearance and disappearance. There is an increased uptake of glucose across the hindlimb; this response appears to be independent of insulin concentrations and may be related to direct effects of TNF. Pyruvate and lactate concentrations rise because of altered central clearance and/or increased production in visceral tissues.",
keywords = "glucose kinetics, glucose metabolism in hindlimb, tumor necrosis factor infusion",
author = "Evans, {D. A.} and Jacobs, {D. O.} and Wilmore, {D. W.}",
year = "1989",
language = "English (US)",
volume = "257",
journal = "American Journal of Physiology - Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "5",

}

TY - JOUR

T1 - Tumor necrosis factor enhances glucose uptake by peripheral tissues

AU - Evans, D. A.

AU - Jacobs, D. O.

AU - Wilmore, D. W.

PY - 1989

Y1 - 1989

N2 - Anesthetized dogs received a constant intravenous infusion of tumor necrosis factor (TNF) or saline over 6 h. Glucose kinetics were studied by determining the rate of glucose turnover and hindlimb substrate flux. Cardiovascular responses were monitored and concentrations of counterregulatory hormones were also measured. TNF infusion caused a fall in blood glucose concentration from 4.6 ± 0.1 to 3.9 ± 0.2 mmol/l by 6 h (P < 0.05). This mild hypoglycemia was associated with increased circulating levels of cortisol, glucagon, and epinephrine. The rate of glucose production increased from 26.5 ± 2.1 to 32.5 ± 0.7 μmol · min-1 · kg body wt-1 (P < 0.05) over the 6-h infusion period; this response was associated with increased glucose disappearance (26.4 ± 2.2 to 32.7 ± 0.9 μmol · min-1 · kg body wt-1, P < 0.05) and enhanced clearance (5.7 ± 0.5 to 9.0 ± 0.6 ml · min-1 · kg body wt-1, P < 0.05). As blood glucose levels fell, hindlimb glucose uptake and glucose clearance increased markedly in TNF-infused animals as compared with controls despite a 50% fall in mean serum insulin concentration. The exchange of lactate, pyruvate, and total amino acid nitrogen across the hindlimbs was similar in both groups of animals. However, arterial concentrations of lactate and pyruvate rose to two to three times their initial values. The hypoglycemia associated with the infusion of TNF results from a disparity between the rate of glucose appearance and disappearance. There is an increased uptake of glucose across the hindlimb; this response appears to be independent of insulin concentrations and may be related to direct effects of TNF. Pyruvate and lactate concentrations rise because of altered central clearance and/or increased production in visceral tissues.

AB - Anesthetized dogs received a constant intravenous infusion of tumor necrosis factor (TNF) or saline over 6 h. Glucose kinetics were studied by determining the rate of glucose turnover and hindlimb substrate flux. Cardiovascular responses were monitored and concentrations of counterregulatory hormones were also measured. TNF infusion caused a fall in blood glucose concentration from 4.6 ± 0.1 to 3.9 ± 0.2 mmol/l by 6 h (P < 0.05). This mild hypoglycemia was associated with increased circulating levels of cortisol, glucagon, and epinephrine. The rate of glucose production increased from 26.5 ± 2.1 to 32.5 ± 0.7 μmol · min-1 · kg body wt-1 (P < 0.05) over the 6-h infusion period; this response was associated with increased glucose disappearance (26.4 ± 2.2 to 32.7 ± 0.9 μmol · min-1 · kg body wt-1, P < 0.05) and enhanced clearance (5.7 ± 0.5 to 9.0 ± 0.6 ml · min-1 · kg body wt-1, P < 0.05). As blood glucose levels fell, hindlimb glucose uptake and glucose clearance increased markedly in TNF-infused animals as compared with controls despite a 50% fall in mean serum insulin concentration. The exchange of lactate, pyruvate, and total amino acid nitrogen across the hindlimbs was similar in both groups of animals. However, arterial concentrations of lactate and pyruvate rose to two to three times their initial values. The hypoglycemia associated with the infusion of TNF results from a disparity between the rate of glucose appearance and disappearance. There is an increased uptake of glucose across the hindlimb; this response appears to be independent of insulin concentrations and may be related to direct effects of TNF. Pyruvate and lactate concentrations rise because of altered central clearance and/or increased production in visceral tissues.

KW - glucose kinetics

KW - glucose metabolism in hindlimb

KW - tumor necrosis factor infusion

UR - http://www.scopus.com/inward/record.url?scp=0024358163&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024358163&partnerID=8YFLogxK

M3 - Article

C2 - 2589544

AN - SCOPUS:0024358163

VL - 257

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 5

ER -