Effect of high-dose endotoxin on glucose production and utilization

Charles H. Lang, Zoltan Spolarics, Aurel Ottlakan, John J. Spitzer

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The purpose of the present study was to determine how a high dose of endotoxin (lipopolysaccharide [LPS]), which produces hypoglycemia, alters in vivo glucose uptake by individual tissues. Catheterized conscious fasted rats were injected intravenously (IV) with either saline, LPS ( 1 mg 100 g body weight [BW], lethal dose [LD] 100), or 3-mercaptopicolinic acid (3-MP), an inhibitor of gluconeogenesis. In the latter two groups, blood glucose levels were clamped at either 6 mmol/L (euglycemia) or 3 mmol/L (hypoglycemia). In the first series of experiments, whole-body glucose flux was determined using [3-3H]glucose, and in the second study in vivo glucose uptake (Rg) by individual tissues was estimated by the tracer [U-14C]-2-deoxyglucose technique. The relative contribution of hypoglycemia per se to the LPS effect was determined by comparing the values from LPS- versus 3-MP-treated animals. There was no difference in the rate of whole-body glucose utilization (Rd) between saline-infused control rats and LPS-treated animals that were hypoglycemic. However, Rg by diaphragm, spleen, liver, and lung was increased in hypoglycemic LPS-treated rats. The increased Rg in these tissues was not observed in 3-MP-treated rats with a comparable hypoglycemia. Only the gastrocnemius muscle showed a reduction in Rg under hypoglycemic conditions, and the decrease was similar in both LPS- and 3-MP-treated animals. When sufficient glucose was infused into LPS-injected rats to maintain euglycemia, whole-body glucose Rd was increased compared with that in hypoglycemic LPS-treated rats. This increase resulted from a normalization of Rg by skeletal muscle as well as an enhanced Rg by diaphragm, spleen, ileum, skin, kidney, and fat. These data indicate that the hypoglycemia produced by high-dose LPS resulted from both an impairment in glucose production and a relative stimulation of glucose disposal by selective tissues. The enhanced Rg by diaphragm, spleen, liver, and lung in LPS-treated rats is masked by the reduction in Rg by skeletal muscle. Although the decreased Rg by gastrocnemius muscle appeared to result from a decrease in blood glucose and/or insulin levels, the enhanced uptake of glucose by other tissues after LPS must have occurred predominantly via a non-insulin-mediated mechanism.

Original languageEnglish (US)
Pages (from-to)1351-1358
Number of pages8
JournalMetabolism
Volume42
Issue number10
DOIs
StatePublished - Oct 1993

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Endotoxins
Lipopolysaccharides
Glucose
Hypoglycemia
Hypoglycemic Agents
Skeletal Muscle
Diaphragm
Spleen
Blood Glucose
Lung
Gluconeogenesis
Liver
Deoxyglucose
Ileum
Fats
Body Weight
Insulin
Kidney
Skin
3-mercaptopicolinic acid

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Lang, Charles H. ; Spolarics, Zoltan ; Ottlakan, Aurel ; Spitzer, John J. / Effect of high-dose endotoxin on glucose production and utilization. In: Metabolism. 1993 ; Vol. 42, No. 10. pp. 1351-1358.
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Lang, CH, Spolarics, Z, Ottlakan, A & Spitzer, JJ 1993, 'Effect of high-dose endotoxin on glucose production and utilization', Metabolism, vol. 42, no. 10, pp. 1351-1358. https://doi.org/10.1016/0026-0495(93)90137-D

Effect of high-dose endotoxin on glucose production and utilization. / Lang, Charles H.; Spolarics, Zoltan; Ottlakan, Aurel; Spitzer, John J.

In: Metabolism, Vol. 42, No. 10, 10.1993, p. 1351-1358.

Research output: Contribution to journalArticle

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AU - Lang, Charles H.

AU - Spolarics, Zoltan

AU - Ottlakan, Aurel

AU - Spitzer, John J.

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N2 - The purpose of the present study was to determine how a high dose of endotoxin (lipopolysaccharide [LPS]), which produces hypoglycemia, alters in vivo glucose uptake by individual tissues. Catheterized conscious fasted rats were injected intravenously (IV) with either saline, LPS ( 1 mg 100 g body weight [BW], lethal dose [LD] 100), or 3-mercaptopicolinic acid (3-MP), an inhibitor of gluconeogenesis. In the latter two groups, blood glucose levels were clamped at either 6 mmol/L (euglycemia) or 3 mmol/L (hypoglycemia). In the first series of experiments, whole-body glucose flux was determined using [3-3H]glucose, and in the second study in vivo glucose uptake (Rg) by individual tissues was estimated by the tracer [U-14C]-2-deoxyglucose technique. The relative contribution of hypoglycemia per se to the LPS effect was determined by comparing the values from LPS- versus 3-MP-treated animals. There was no difference in the rate of whole-body glucose utilization (Rd) between saline-infused control rats and LPS-treated animals that were hypoglycemic. However, Rg by diaphragm, spleen, liver, and lung was increased in hypoglycemic LPS-treated rats. The increased Rg in these tissues was not observed in 3-MP-treated rats with a comparable hypoglycemia. Only the gastrocnemius muscle showed a reduction in Rg under hypoglycemic conditions, and the decrease was similar in both LPS- and 3-MP-treated animals. When sufficient glucose was infused into LPS-injected rats to maintain euglycemia, whole-body glucose Rd was increased compared with that in hypoglycemic LPS-treated rats. This increase resulted from a normalization of Rg by skeletal muscle as well as an enhanced Rg by diaphragm, spleen, ileum, skin, kidney, and fat. These data indicate that the hypoglycemia produced by high-dose LPS resulted from both an impairment in glucose production and a relative stimulation of glucose disposal by selective tissues. The enhanced Rg by diaphragm, spleen, liver, and lung in LPS-treated rats is masked by the reduction in Rg by skeletal muscle. Although the decreased Rg by gastrocnemius muscle appeared to result from a decrease in blood glucose and/or insulin levels, the enhanced uptake of glucose by other tissues after LPS must have occurred predominantly via a non-insulin-mediated mechanism.

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