Glucose-induced suppression of endogenous glucose production: dynamic response to differing glucose profiles

Abstract

To determine whether, in the presence of constant insulin concentrations, a change in glucose concentrations results in a reciprocal change in endogenous glucose production (EGP), glucagon (∼130 ng/l) and insulin (∼65 pmol/l) were maintained at constant “basal” concentrations while glucose was clamped at ∼5.3 mM (euglycemia), ∼7.0 mM (sustained hyperglycemia; n = 10), or varied to create a “postprandial” profile (profile; n = 11). EGP fell slowly over the 6 h of the euglycemia study. In contrast, an increase in glucose to 7.13 ± 0.3 mmol/l resulted in prompt and sustained suppression of EGP to 9.65 ± 1.21 μmol·kg-1 · min-1. On the profile study day, glucose increased to a peak of 11.2 ± 0.5 mmol/l, and EGP decreased to a nadir of 6.79 ± 2.54 μmol · kg-1 · min-1 by 60 min. Thereafter, the fall in glucose was accompanied by a reciprocal rise in EGP to rates that did not differ from those observed on the euglycemic study day (11.31 ± 2.45 vs. 12.11 ± 3.21 μmol · kg-1 · min-1). Although the pattern of change of glucose differed markedly on the sustained hyperglycemia and profile study days, by design the area above basal did not. This resulted in equivalent suppression of EGP below basal (-1,952 ± 204 vs. -1,922 ± 246 mmol · kg-1 · 6 h-1). These data demonstrate that, in the presence of a constant basal insulin concentration, changes in glucose within the physiological range rapidly and reciprocally regulate EGP.