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Am J Physiol Endocrinol Metab 285: E819-E826, 2003; doi:10.1152/ajpendo.00145.2003
0193-1849/03 $5.00
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Relative importance of liver, kidney, and substrates in epinephrine-induced increased gluconeogenesis in humans

Christian Meyer,1,2 Michael Stumvoll, Stephen Welle, Hans J. Woerle, Morey Haymond,3 and John Gerich1

1Departments of Medicine, University of Rochester School of Medicine, Rochester, New York 14642; 2Carl T. Hayden Veterans Affairs Medical Center, Phoenix, Arizona 85012; and 3Baylor College of Medicine, Children's Nutrition Research Center, Houston, Texas 77030

Submitted 4 April 2003 ; accepted in final form 6 June 2003

Splanchnic and renal net balance measurements indicate that lactate and glycerol may be important precursors for epinephrine-stimulated gluconeogenesis (GNG) in liver and kidney, but the effects of epinephrine on their renal and hepatic conversion to glucose in humans have not yet been reported. We therefore used a combination of renal balance and isotopic techniques in nine postabsorptive volunteers to measure systemic and renal GNG from these precursors before and during a 3-h infusion of epinephrine (270 pmol · kg1 · min1) and calculated hepatic GNG as the difference between systemic and renal rates. During infusion of epinephrine, renal and hepatic GNG from lactate increased 4- to 6-fold and accounted for ~85 and 70% of renal and hepatic glucose release, respectively, at the end of study; renal and hepatic GNG from glycerol increased ~1.5- to 2-fold and accounted for ~7–9% of renal and hepatic glucose release at the end of study. The increased renal GNG from lactate and glycerol was due not only to their increased renal uptake (~3.3- and 1.4-fold, respectively) but also increased renal gluconeogenic efficiency (~1.8- and 1.5-fold). The increased renal uptake of lactate and glycerol was wholly due to their increased arterial concentrations, since their renal fractional extraction remained unchanged and renal blood flow decreased. We conclude that 1) lactate is the predominant precursor for epinephrine-stimulated GNG in both liver and kidney, 2) hepatic and renal GNG from lactate and glycerol are similarly sensitive to stimulation by epinephrine, and 3) epinephrine increases renal GNG from lactate and glycerol by increasing substrate availability and the gluconeogenic efficiency of the kidney.

glycerol; lactate; glycogenolysis; tracer



Address for reprint requests and other correspondence: C. Meyer, Carl T. Hayden VA Medical Center, Dept. of Endocrinology, 650 East Indian School Rd., Phoenix, AZ 85012 (E-mail: christian.meyer{at}med.va.gov).







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