Thiamin deficiency impairs endotoxin-induced increases in hepatic glucose output.
We addressed the role of thiamin, a cofactor for several enzymes involved in glucose metabolism, in the glucose metabolic response to endotoxin. Characterized by hyperglycemia, increased hepatic glucose production exceeding elevated rates of whole-body glucose utilization, this response is mediated by hormones and cytokines and is dependent on the immune and nutritional status of the host. We hypothesized that a thiamin-deficient state would impair the metabolic response to endotoxin. Rats were fed a thiamin-deficient or control diet for 6 wk before in vivo assessment of glucose kinetics. In control rats, Escherichia coli endotoxin increased the rate of glucose appearance (+76%), disappearance (+70%), and metabolic clearance (+50%). Thiamin deficiency resulted in increased plasma glucose (18%) and lactate (3- to 4-fold) as well as in a 30% decrease in insulin and an increase in glucagon (2.6-fold) and corticosterone (3.6-fold). Thiamin deficiency inhibited the endotoxin-induced hyperglycemia and the rise in hepatic glucose production, glucose utilization, and metabolic clearance rate.
Molina
P E
PE
Department of Surgery, State University of New York, Stony Brook 11794-8191.
Yousef
K A
KA
Smith
R M
RM
Tepper
P G
PG
Lang
C H
CH
Abumrad
N N
NN
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004731:Endotoxins / Q000494:pharmacology*; D002149:Energy Intake; D004926:Escherichia coli; D005508:Food Deprivation; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D017207:Rats, Sprague-Dawley; D013832:Thiamine Deficiency / Q000378:metabolism*
D001786:Blood Glucose; D004731:Endotoxins; D007328:Insulin; D008112:Liver Glycogen; D005947:Glucose