In vivo glucose metabolism in the awake rat: tracer and insulin clamp studies.
The goals of this study were twofold: (1) to determine the in vivo dose-response relationship in the conscious, unstressed rat between the plasma insulin concentration and total body glucose uptake, and between plasma insulin and suppression of endogenous glucose production; and (2) to develop a physiologic compartmental model to describe the kinetics of plasma glucose in the rat in the basal state. In order to perform repeat insulin clamp studies in the same rat, chronic catheters were implanted in the aortic arch (via the carotid artery) and in the cardiac atrium (via the jugular vein), exteriorized, and fixed to the back of the skull with a dental cement cap. Insulin was infused at rates of 1.2, 2.4, 4.8, 12, and 24 mU/min.kg, and the plasma glucose was held constant at the basal level by a variable glucose infusion (euglycemic insulin clamp). The resulting steady-state plasma insulin concentrations ranged from 40 to 1,300 microU/mL. The dose-response curve for glucose uptake was sigmoidal in shape: in the basal state, total glucose utilization averaged 6.8 mg/min.kg at an insulin concentration of 9 microU/mL, half-maximal glucose uptake (18.3 mg/kg.min) occurred at a plasma insulin concentration between 70 and 80 microU/mL, and maximal uptake (36.6 mg/kg.min) was seen at an insulin level in excess of 100 microU/mL. Residual endogenous glucose production was evaluated by a prime-continuous infusion of (3-3H)-glucose. The dose-response curve for suppression of endogenous glucose output also was sigmoidal.(ABSTRACT TRUNCATED AT 250 WORDS)
Smith
D
D
Department of Medicine, Yale University School of Medicine, New Haven, CT 06510.
Rossetti
L
L
Ferrannini
E
E
Johnson
C M
CM
Cobelli
C
C
Toffolo
G
G
Katz
L D
LD
DeFronzo
R A
RA
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003243:Consciousness; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics; D006706:Homeostasis; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007332:Insulin Infusion Systems; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose