TY - JOUR
T1 - Effect of high-dose endotoxin on glucose production and utilization
AU - Lang, Charles H.
AU - Spolarics, Zoltan
AU - Ottlakan, Aurel
AU - Spitzer, John J.
N1 - Funding Information:
From the Department of Physiology, Louisiana State University Medicat Center, New Orleans, LA. Submitted September 15, 1992; accepted November IO, 1992. Supported by National Instifutes of Health Grants No. GM 38032 and GM 32654. Address reprint requesfs to Charles H. Lang, PhD, Director of Surgical Research, Department of Surgery, SUNY at Stony Brook, Stony Brook, NY 11794-8191. Copyrighf 0 1993 by W.B. Saunders Company 0026-0495/93/4210-0020$03.00o$oj.oo/0
PY - 1993/10
Y1 - 1993/10
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.
AB - 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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U2 - 10.1016/0026-0495(93)90137-D
DO - 10.1016/0026-0495(93)90137-D
M3 - Article
C2 - 8412750
AN - SCOPUS:0027517416
SN - 0026-0495
VL - 42
SP - 1351
EP - 1358
JO - Metabolism
JF - Metabolism
IS - 10
ER -
