The role of the central nervous system in modulating glucose and protein metabolism during insulin-induced hypoglycemia.
We previously established that insulin-induced hypoglycemia is associated with enhanced proteolysis with the GI tract being the major contributor to this response. In the present study we examined whether brain hypoglycemia modulates the changes in amino acid and glucose kinetics during insulin-induced hypoglycemia. Studies were performed in 24 h faster conscious dogs chronically fitted with catheters in the femoral artery, portal vein, hepatic vein, femoral vein and in both carotid and vertebral arteries, and that were also fitted with permanent tracheostomies. Following a 30 min basal period insulin was infused i.v. at 300 mU/kg.h to achieve systemic hypoglycemia averaging 42 +/- 2 mg/dl. In group I (n = 6) both central and systemic (global) hypoglycemia was allowed to develop. The rate of net hepatic glucose output (NHGO) increased by 50% above basal. Plasma leucine increased from 120 +/- 12 mumol/l basally to 154 +/- 30 mumol/l during the last hour of hypoglycemia. The rate of leucine appearance into the plasma compartment (R(a)) increased from 154 +/- 30 to 200 +/- 36 mumol/kg.h and its rate of oxidation increased from 22 +/- 5 to 51 +/- 8 mumol/kg.h, while its non-oxidative rate of disposal (141 +/- 12 mumol/kg.h) did not change. Net leucine balance across the gut was neutral (6 +/- 5 mumol/kg.h) and switched to net output of 96 +/- 24 mumol/kg.h. In group II (n = 5) 10% dextrose in water was infused into both carotid and vertebral arteries to prevent profound CNS glucopenia. This was associated with a drop in NHGO.(ABSTRACT TRUNCATED AT 250 WORDS)
Hourani
H
H
Department of Surgery, Bowman Gray School of Medicine, Nashville, TN.
Lacy
B
B
Eltayeb
K
K
Abumrad
N N
NN
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002339:Carotid Arteries; D002490:Central Nervous System / Q000502:physiology*; D004285:Dogs; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D006614:Hindlimb / Q000378:metabolism; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism*; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007930:Leucine / Q000097:blood / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D011506:Proteins / Q000378:metabolism*; D014711:Vertebral Artery
D001786:Blood Glucose; D007328:Insulin; D011506:Proteins; D007930:Leucine; D005947:Glucose