Renal substrate exchange and gluconeogenesis in normal postabsorptive humans

Meyer, Christian; Stümvoll, Michael; Dostou, Jean M.; Welle, Stephen; Haymond, Morey W.; Gerich, John E.

doi:10.1152/ajpendo.00116.2001

Cited by 126 publications

(103 citation statements)

References 52 publications

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“…However, the increase in urea production in the lactating women might also indicate an increase in hepatic gluconeogenesis. Presumably, both glycerol (a product of lipolysis) (24,26) and amino acids (8,17) provide the carbon needed for the hepatic gluconeogenesis. However, it is impossible to determine the veracity of this argument without considerably more invasive studies.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms to conserve glucose in lactating women during a 42-h fast

Mohammad

Sunehag

Chacko

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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Mohammad MA, Sunehag AL, Chacko SK, Pontius AS, Maningat PD, Haymond MW. Mechanisms to conserve glucose in lactating women during a 42-h fast. Am J Physiol Endocrinol Metab 297: E879 -E888, 2009. First published August 4, 2009 doi:10.1152/ajpendo.00364.2009Little is known about how lactating women accommodate for their increased glucose demands during fasting to avoid maternal hypoglycemia. The objective of this study was to determine whether lactating women conserve plasma glucose by reducing maternal glucose utilization by increasing utilization of FFA and ketone bodies and/or increasing gluconeogenesis and mammary gland hexoneogenesis. Six healthy exclusively breastfeeding women and six nonlactating controls were studied during 42 h of fasting and 6 h of refeeding. Glucose and protein kinetic parameters were measured using stable isotopes and GCMS and energy expenditure and substrate oxidation using indirect calorimetry. After 42 h of fasting, milk production decreased by 16% but remained within normal range. Glucose, insulin, and C-peptide concentrations decreased with the duration of fasting in both groups but were lower (P Ͻ 0.05) in lactating women. Glucagon, FFA, and ␤-hydroxybutyrate concentrations increased with fasting time (P Ͻ 0.001) and were higher (P Ͻ 0.0001) in lactating women during both fasting and refeeding. During 42 h of fasting, gluconeogenesis was higher in lactating women compared with nonlactating controls (7.7 Ϯ 0.4 vs. 6.5 Ϯ 0.2 mol⅐kg Ϫ1 ⅐min Ϫ1, P Ͻ 0.05), whereas glycogenolysis was suppressed to similar values (0.4 Ϯ 0.1 vs. 0.9 Ϯ 0.2 mol⅐kg Ϫ1 ⅐min Ϫ1 , respectively). Mammary hexoneogenesis did not increase with the duration of fasting. Carbohydrate oxidation was lower and fat and protein oxidations higher (P Ͻ 0.05) in lactating women. In summary, lactating women are at risk for hypoglycemia if fasting is extended beyond 30 h. The extra glucose demands of extended fasting during lactation appear to be compensated by increasing gluconeogenesis associated with ketosis, decreasing carbohydrate oxidation, and increasing protein and FFA oxidations. stable isotopes; gluconeogenesis; lactation; milk; production USING NEW TECHNIQUES TO MEASURE GLUCONEOGENESIS in vivo, we (4,12,18,30) and others (13, 15) demonstrated that gluconeogenesis accounts for ϳ50% (ranging from 35 to 75%) of glucose production following an overnight fast. During carbohydrate (CHO) absorption, plasma glucose and insulin concentrations increase simultaneously, but plasma glucose concentrations remain in a very narrow range in normal individuals. This fine control is mediated by glucose-induced increase in plasma insulin, leading to increasing peripheral glucose utilization and glycogen synthesis, whereas hepatic glucose production is decreasing as a result of inhibited glycogenolysis (22). In contrast, during fasting, plasma glucose and insulin concentrations decrease and plasma FFA, ketone bodies, and glucagon concentrations increase (22), resulting in decreased glucose utilization and/or potentially increased glu...

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Section: Discussionmentioning

confidence: 99%

Mechanisms to conserve glucose in lactating women during a 42-h fast

Mohammad

Sunehag

Chacko

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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“…Although approximately 20% of the plasma glutamine is filtered, the measured rat renal arterial-venous difference is ,3% of the arterial concentration of glutamine (61), and only 7% of the plasma glutamine is extracted by the human kidneys even after an overnight fast (62). Therefore, renal utilization is significantly less than the fraction of plasma glutamine filtered by the glomeruli.…”

Section: Response To Acidosismentioning

confidence: 93%

Proximal Tubule Function and Response to Acidosis

Curthoys

Moe

2014

Clinical Journal of the American Society of Nephrology

257

193

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SummaryThe human kidneys produce approximately 160-170 L of ultrafiltrate per day. The proximal tubule contributes to fluid, electrolyte, and nutrient homeostasis by reabsorbing approximately 60%-70% of the water and NaCl, a greater proportion of the NaHCO 3 , and nearly all of the nutrients in the ultrafiltrate. The proximal tubule is also the site of active solute secretion, hormone production, and many of the metabolic functions of the kidney. This review discusses the transport of NaCl, NaHCO 3 , glucose, amino acids, and two clinically important anions, citrate and phosphate. NaCl and the accompanying water are reabsorbed in an isotonic fashion. The energy that drives this process is generated largely by the basolateral Na 1 /K 1 -ATPase, which creates an inward negative membrane potential and Na 1 -gradient. Various Na 1 -dependent countertransporters and cotransporters use the energy of this gradient to promote the uptake of HCO 3 2 and various solutes, respectively. A Na 1 -dependent cotransporter mediates the movement of HCO 3 2 across the basolateral membrane, whereas various Na 1 -independent passive transporters accomplish the export of various other solutes. To illustrate its homeostatic feat, the proximal tubule alters its metabolism and transport properties in response to metabolic acidosis. The uptake and catabolism of glutamine and citrate are increased during acidosis, whereas the recovery of phosphate from the ultrafiltrate is decreased. The increased catabolism of glutamine results in increased ammoniagenesis and gluconeogenesis. Excretion of the resulting ammonium ions facilitates the excretion of acid, whereas the combined pathways accomplish the net production of HCO 3 2 ions that are added to the plasma to partially restore acid-base balance.

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“…None of the subjects were vegetarians or followed a creatine-restricted diet. Renal net balance measurements were performed as previously described (16). Briefly, subjects were admitted to the University of Rochester General Clinical Research Center between 6 and 7 PM on the evening before experimentation.…”

Section: Methodsmentioning

confidence: 99%

Creatine synthesis: production of guanidinoacetate by the rat and human kidney in vivo

Edison¹,

Brosnan²,

Meyer³

et al. 2007

American Journal of Physiology-Renal Physiology

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Edison EE, Brosnan ME, Meyer C, Brosnan JT. Creatine synthesis: production of guanidinoacetate by the rat and human kidney in vivo. Am J Physiol Renal Physiol 293: F1799-F1804, 2007. First published October 10, 2007; doi:10.1152/ajprenal.00356.2007.-A fraction of the body's creatine and creatine phosphate spontaneously degrades to creatinine, which is excreted by the kidneys. In humans, this amounts to ϳ1-2 g/day and demands a comparable rate of de novo creatine synthesis. This is a two-step process in which L-arginine:glycine amidinotransferase (AGAT) catalyzes the conversion of glycine and arginine to ornithine and guanidinoacetate (GAA); guanidinoacetate methyltransferase (GAMT) then catalyzes the S-adenosylmethioninedependent methylation of GAA to creatine. AGAT is found in the kidney and GAMT in the liver, which implies an interorgan movement of GAA from the kidney to the liver. We studied the renal production of this metabolite in both rats and humans. In control rats, [GAA] was 5.9 M in arterial plasma and 10.9 M in renal venous plasma for a renal arteriovenous (A-V) difference of Ϫ5.0 M. In the rat, infusion of arginine or citrulline markedly increased renal GAA production but infusion of glycine did not. Rats fed 0.4% creatine in their diet had decreased renal AGAT activity and mRNA, an arterial plasma [GAA] of 1.5 M, and a decreased renal A-V difference for GAA of Ϫ0.9 M. In humans, [GAA] was 2.4 M in arterial plasma, with a renal A-V difference of Ϫ1.1 M. These studies show, for the first time, that GAA is produced by both rat and human kidneys in vivo. L-arginine:glycine amidinotransferase; transamidinase; amino acid metabolism CREATINE AND CREATINE PHOSPHATE act to buffer the cytosolic ATP/ADP ratio in tissues that have high and variable rates of ATP usage (e.g., skeletal and cardiac muscle). Creatine kinase catalyzes the reversible transfer of the ␥-phosphate group of ATP to the guanidino group of creatine to yield ADP and creatine phosphate.ATP ϩ Creatine 7 ADP ϩ Creatine Phosphate (Equation 1) In skeletal muscle, creatine kinase activity is high, keeping its reaction at near-equilibrium. This keeps the ADP and ATP concentrations fairly constant and buffers the cytosolic phosphorylation potential (18,27,28). Energy storage and transmission by the creatine kinase system are hypothesized to work in two ways: as a temporal buffer and as a spatial buffer. The temporal energy buffer theory is best exemplified during episodes of high-energy use, such as muscle contraction. As soon as ATP is hydrolyzed, it must be replenished. The high-energy phosphate of creatine phosphate is transferred to ADP to regenerate ATP. This leads to an accumulation of creatine that must be rephosphorylated during recovery from exercise. The spatial energy buffer theory implies that creatine phosphate acts as an energy carrier, working to transport high-energy phosphate from sites of synthesis (mitochondria) to sites of ATP utilization in the cytosol (27

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Renal substrate exchange and gluconeogenesis in normal postabsorptive humans

Cited by 126 publications

References 52 publications

Mechanisms to conserve glucose in lactating women during a 42-h fast

Mechanisms to conserve glucose in lactating women during a 42-h fast

Proximal Tubule Function and Response to Acidosis

Creatine synthesis: production of guanidinoacetate by the rat and human kidney in vivo

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