AJP - Endocrinology and Metabolism, Vol 248, Issue 6 648-E655, Copyright © 1985 by American Physiological Society
Indomethacin and salicylate modulate effect of insulin on glucose kinetics in dogs
J. D. Miller, S. Ganguli and M. A. Sperling
We studied insulin's effects on glucose production (Ra) and utilization
(Rd) in trained, conscious dogs before and during treatment with
indomethacin (Indo) and salicylate (S). Ra and Rd (mg X kg-1 X min-1) were
calculated by isotope dilution using [3-3H]glucose. Animals were treated
with either oral Indo or acetylsalicylic acid for 1 day before the
respective studies. On the study day, experimental animals were given a
continuous infusion of either saline (control), Indo (5 mg/kg bolus
followed by 0.05 mg X kg-1 X min-1), or sodium salicylate (0.45 mg X kg-1 X
min-1) for 330 min on separate days; each animal participated in all three
protocols. After establishing steady-state specific activity, control (C)
and experimental animals (n = 6/group) received insulin, 0.275 mU X kg-1 X
min-1 for 150 min, raising serum insulin levels two- to threefold above
basal. During insulin infusion in C, plasma glucose (G) fell from 99 +/- 2
to 82 +/- 6 ml/dl (P less than 0.01), associated with a transient fall in
Ra from 2.5 +/- 0.3 to 1.9 +/- 0.2 (P less than 0.01) at 30 min, returning
to base line at 45 min; Rd did not change. In the Indo and S groups, G also
fell by a similar extent. In contrast to C, however, the fall in G was
associated with a rise in Rd, commencing at 30 min in the Indo group (P
less than 0.05) and at 45 min in the S group (P less than 0.01); Ra did not
fall and actually rose above basal (P less than 0.05), although it did not
match the rise in Rd.(ABSTRACT TRUNCATED AT 250 WORDS)
