Relative importance of liver, kidney, and substrates in epinephrine-induced increased gluconeogenesis in humans

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.

Expression of mRNA for glucose transport proteins in jejunum, liver, kidney and skeletal muscle of pigs

“…The intestinal entry of glucose is supported by de novo synthesis (i.e. gluconeogenesis) in liver and kidney, which can adapt to glucose demand and glucogenic precursor supply (37,39). The liver additionally stores glucose as glycogen for periods of increased glucose demand (47).…”

Renal lactate elimination is maintained during moderate exercise in humans

“…Since the concentration of erythropoietin in renal venous blood was unrelated to the induced reduction in renal blood flow, the reduction in renal blood flow was unlikely to be critical for renal tissue metabolism. Meyer et al (2003) found that lactate is the predominant precursor for epinephrine-stimulated gluconeogenesis in both the liver and the kidney, and that increased gluconeogenesis from lactate is due mainly to elevated substrate availability and improved gluconeogenic efficiency. Supposedly, the arterial plasma epinephrine concentration would be *4 mmol Á L 71 at the exercise intensity chosen for this study (Kjaer, Engfred, Fernandes, Secher, & Galbo, 1993) and, thereby, sufficient to stimulate elimination of lactate from the kidney (Meyer et al, 2003).…”

“…Kidney lactate uptake may represent 20-30% of the systemic lactate clearance, and the kidneys are considered to be second only to the liver in eliminating lactate from the circulation (Bellomo, 2002). In contrast, the lactate taken up by the kidneys contributes to renal gluconeogenesis (Cersosimo, Garlick, & Ferretti, 2000) and, since it is stimulated by adrenaline (Meyer et al, 2003) that increases disproportionately with exercise intensity (Kjaer, 1989), kidney lactate elimination may be robust to physical activity (Tidgren et al, 1991).…”

Hypoglycemia in Critically Ill Patients

“…The kidney is responsible for approximately 20% of the glucose production under resting conditions (Meyer et al, 2002). During stress, however, cathecholamines can increase the renal contribution to glucose production up to 40% by increasing substrate availability and the gluconeogenic efficiency of the kidney (Meyer et al, 2003). Glucagon increases both gluconeogenesis and glycogenolysis in the liver, but has no effect on the kidney.…”