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Failure of complete suppression of endogenous glucose production by euglycaemic hyperinsulinaemia in normal humans
Author(s) -
NEELY R. D. G.,
HARPER R.,
ROONEY D. P.,
ENNIS C. N.,
BELL P. M.,
TRIMBLE E. R.
Publication year - 1995
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1995.tb01728.x
Subject(s) - medicine , endocrinology , basal (medicine) , insulin , glucose clamp technique , endogeny , hyperinsulinemia , insulin resistance , pancreatic hormone , chemistry , biology
. In normal subjects, endogenous glucose production (EGP) is usually assumed to be completely suppressed during euglycaemic clamp studies performed at high insulin levels (>100 mU L ‐1 ). However, this assumption is based on non‐steady‐state tracer measurements of EGP which are prone to negative errors. We have used purified [6‐ 3 H]glucose in an optimal tracer infusion protocol to assess the suppression of EGP during 4 h euglycaemic clamps in eight normal men. An insulin infusion rate of 5 mU kg ‐1 min ‐1 was chosen to achieve supraphysiological (> 500 mU L ‐1 ) plasma insulin concentrations. Using a labelled exogenous glucose infusion, plasma glucose (mean ± SEM 5.3 ± 0.1 mmol L ‐1 ) and glucose specific activities (mean 100 ± 3% of basal) were maintained constant from 80 to 240 min. During hyperinsulinaemia, isotopically determined glucose appearance rates (Ra) were greater than glucose infusion rates (GIR) throughout the euglycaemic clamp period ( P <0.001) and EGP (Ra‐GIR) was always greater than zero. In seven of the eight subjects studied EGP was partly suppressed but showed a wide variation (EGP 5 to 91% of basal at 80–120 min and 12 to 87% of basal at 200–240 min) while in one subject EGP rose above basal (by 72% at 80–120 min and 49% at 200–240 min). We conclude that EGP is not completely suppressed during euglycaemic clamps at high insulin levels.