Effect of high-dose endotoxin on glucose production and utilization.
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 (i.v.) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Lang
C H
CH
Department of Physiology, Louisiana State University Medical Center, New Orleans.
Spolarics
Z
Z
Ottlakan
A
A
Spitzer
J J
JJ
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D005934:Glucagon / Q000032:analysis / Q000097:blood / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007003:Hypoglycemia / Q000097:blood / Q000378:metabolism; D007082:Ileum / Q000737:chemistry / Q000378:metabolism; D007275:Injections, Intravenous; D007328:Insulin / Q000032:analysis / Q000097:blood / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000737:chemistry / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000737:chemistry / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000037:antagonists & inhibitors; D010848:Picolinic Acids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000737:chemistry / Q000378:metabolism; D013154:Spleen / Q000737:chemistry / Q000378:metabolism; D014316:Tritium
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D004731:Endotoxins; D007328:Insulin; D008070:Lipopolysaccharides; D010848:Picolinic Acids; D014316:Tritium; C008363:3-mercaptopicolinic acid; D005934:Glucagon; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose