MODERATE DECLINE IN SPECIFIC ACTIVITY DOES NOT LEAD TO AN UNDERESTIMATION OF HEPATIC GLUCOSE-PRODUCTION DURING A GLUCOSE CLAMP

We have previously shown that modeling errors lead to underestimation of hepatic glucose production (HGP) during glucose clamps when specifi c activity (SA) declines markedly. We wished to assess whether the fai lure to keep SA constant substantially affects calculation of HGP duri ng insulin infusion when glucose requirements to maintain the glucose clamp are moderate. Therefore, 150-minute hyperinsulinemic (5.4 pmol . kg(-1). min(-1)) clamps were performed in depancreatized dogs that we re maintained hyperglycemic (similar to 10 mmol/L) with either(1) unla beled glucose infusate (COLD Ginf, n = 5) or (2) labeled glucose infus ate (HOT Ginf, n = 6) containing high-performance liquid chromatograph y (HPLC) purified [6-H-3]glucose. Insulinemia and glucagonemia were si milar between the two groups. Additionally, glucose infusion rates wer e equivalent with COLD and HOT Ginf, indicating comparable insulin eff ects on overall glucose metabolism. The SA decreased a maximum of 32% with COLD Ginf, but remained constant with HOT Ginf. HGP was suppresse d equally with COLD or HOT Ginf treatments at each time point during t he clamp (mean suppression during last hour of clamp, 69% +/- 4% and 6 9% +/- 5%, P = NS, COLD and HOT Ginf, respectively). We conclude that when glucose requirements are moderate and SA changes slowly, as in th e diabetic dog, it is not necessary to keep SA perfectly constant to a void significant modeling errors when calculating HPG during hyperinsu linemic clamps. (C) 1996 by W.B. Saunders Company.