Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/6/2003
Publication Date: 10/1/2003
Citation: Meyer, C., Stumvoll, M., Welle, S., Woerle, H.J., Haymond, M., Gerich, J. 2003. Relative importance of liver, kidney and substrates in epinephrine-induced increased gluconeogenesis in humans. American Journal of Physiology - Endocrinology and Metabolism. 285:E819-E826. Interpretive Summary: Consistent with the view that renal glucose release is normally exclusively due to gluconeogenesis, the combination of our data from the present and our previous report indicates that the sum of renal gluconeogenesis from lactate, glycerol, glutamine, and alanine can account for all of the renal glucose release during epinephrine infusion. It is of interest to note that these combined data also indicate that the sum of hepatic gluconeogenesis from these precursors can account for virtually all of hepatic glucose release at the end of the 180-min epinephrine infusion. Although one should interpret the data with caution, since gluconeogenesis from different precursors were determined in different subjects, our findings are in close agreement with those of previous net splanchnic balance measurements in dogs and humans under similar experimental conditions. In conclusion, our findings in post-absorptive humans indicate that, during hyperepinephrinemia: 1) liver accounts for approximately 60% and kidney for 40% of the increased gluconeogenesis; 2) lactate is the principal gluconeogenic precursor for both liver and kidney; and 3) the increased renal gluconeogenesis is due to increased substrate availability and greater renal gluconeogenic efficiency.
Technical Abstract: 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/kg-1/ min-1) 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 approximately 85 and 70% of renal and hepatic glucose release, respectively, at the end of study; renal and hepatic GNG from glycerol increased approximately 1.5- to 2-fold and accounted for approximately 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 (approximately 3.3- and 1.4-fold, respectively) but also increased renal gluconeogenic efficiency (approximately 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.