A moderate decline in specific activity does not lead to an underestimation of hepatic glucose production during a glucose clamp

Simon J. Fisher, Zhi Q. Shi, H. Lavina A. Lickley, Suad Efendic, Mladen Vranic, Adria Giacca

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26 Scopus citations


We have previously shown that modeling errors lead to underestimation of hepatic glucose production (HGP) during glucose clamps when specific activity (SA) declines markedly. We wished to assess whether the failure to keep SA constant substantially affects calculation of HGP during 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 were maintained hyperglycemic (~10 mmol/L) with either (1) unlabeled glucose infusate (COLD Ginf, n = 5) or (2) labeled glucose infusate (HOT Ginf, n = 6) containing high-performance liquid chromatography (HPLC) purified [6-3H]glucose. Insulinemia and glucagonemia were similar between the two groups. Additionally, glucose infusion rates were equivalent with COLD and HOT Ginf, indicating comparable insulin effects on overall glucose metabolism. The SA decreased a maximum of 32% with COLD Ginf, but remained constant with HOT Ginf. HGP was suppressed equally with COLD or HOT Ginf treatments at each time point during the clamp (mean suppression during last hour of clamp, 69% ± 4% and 69% ± 5%, P = NS, COLD and HOT Ginf, respectively). We conclude that when glucose requirements are moderate and SA changes slowly, as in the diabetic dog, it is not necessary to keep SA perfectly constant to avoid significant modeling errors when calculating HPG during hyperinsulinemic clamps.

Original languageEnglish
Pages (from-to)587-593
Number of pages7
JournalMetabolism: Clinical and Experimental
Issue number5
StatePublished - 1996

Bibliographical note

Funding Information:
From the Departments of Physiology, Surgery, and Medicine, University of Toronto, Toronto; Women's College Hospital, Toronto, Ontario, Canada; and Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden. Submitted May 3, 1995; accepted September 2, 1995. Supported by the Canadian Diabetes Association (CDA), Juvenile Diabetes Foundation (JDF), and the Medical Research Council (MRC) of Canada. S.J.F. was supported by a CDA studentship and is currently supported by a MRC studentship. Z.Q.S. was supported by the CDA. A.G. was supported by fellowships from the San Raffaele Institute, (Milan, Italy), the JDF, and the CDA, and is currently a recipient of a Career Development Award from the JDF. Address reprint requests to Mladen Vranic, MD, DSc, Professor and Chairman of Physiology, Professor of Medicine, Medical Sciences Building, Room 3358, University of Toronto, Toronto, Ontario, Canada M5S 1A8. Copyright © 1996 by W.B. Saunders Company 0026-0495/96/4505-0008503.00/0

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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