The relationship between gluconeogenic substrate supply and glucose production in humans

1990 ◽  
Vol 258 (2) ◽  
pp. E288-E296 ◽  
Author(s):  
F. Jahoor ◽  
E. J. Peters ◽  
R. R. Wolfe

The relationship between gluconeogenic precursor supply and glucose production has been investigated in 14-h and 86-h fasted humans. In protocols 1 and 2 [6,6-2H]glucose and [15N2]urea were infused to measure glucose and urea production rates (Ra) in response to infusions of glycerol and alanine. In protocol 3 first [15N]alanine, [3-13C]lactate, and [6,6-2H]glucose were infused before and during administration of dichloroacetate (DCA) to determine the response of glucose Ra to decreased fluxes of pyruvate, alanine, and lactate, then alanine was infused with DCA and glucose Ra measured. After a 14-h fast, neither alanine nor glycerol increased glucose Ra. Basal glucose Ra decreased by one-third after 86 h of fasting, yet glycerol and alanine infusions had no effect on glucose Ra. Glycerol always reduced urea Ra (P less than 0.05), suggesting that glycerol competitively inhibited gluconeogenesis from amino acids. DCA decreased the fluxes of pyruvate, alanine (P less than 0.01), and glucose Ra (P less than 0.01), which was prevented by alanine infusion. These findings suggest that 1) the reduction in glucose Ra after an 86-h fast is not because of a shortage of gluconeogenic substrate; 2) nonetheless, the importance of precursor supply to maintain basal glucose Ra is confirmed by the response to DCA; 3) an excess of one gluconeogenic substrate inhibits gluconeogenesis from others.

2019 ◽  
Vol 20 (7) ◽  
pp. 644-651 ◽  
Author(s):  
Changsong Gu ◽  
Xiangbing Mao ◽  
Daiwen Chen ◽  
Bing Yu ◽  
Qing Yang

Branched chain amino acids are the essential nutrients for humans and many animals. As functional amino acids, they play important roles in physiological functions, including immune functions. Isoleucine, as one of the branched chain amino acids, is also critical in physiological functions of the whole body, such as growth, immunity, protein metabolism, fatty acid metabolism and glucose transportation. Isoleucine can improve the immune system, including immune organs, cells and reactive substances. Recent studies have also shown that isoleucine may induce the expression of host defense peptides (i.e., β-defensins) that can regulate host innate and adaptive immunity. In addition, isoleucine administration can restore the effect of some pathogens on the health of humans and animals via increasing the expression of β-defensins. Therefore, the present review will emphatically discuss the effect of isoleucine on immunity while summarizing the relationship between branched chain amino acids and immune functions.


1984 ◽  
Vol 38 (2) ◽  
pp. 177-179 ◽  
Author(s):  
B.S. Chauhan ◽  
N.C. Desai ◽  
Ramesh Bhatnagar ◽  
S.P. Garg

1991 ◽  
Vol 260 (3) ◽  
pp. E453-E458 ◽  
Author(s):  
Y. Ohtake ◽  
M. G. Clemens

This study was performed to investigate the interrelationship between gluconeogenesis and ureagenesis during sepsis. In isolated perfused livers, gluconeogenesis was assessed using either lactate or a combination of lactate, glutamine, and alanine as substrate. Ureagenesis was assessed using either NH4Cl or glutamine plus alanine as substrate. NH4Cl stimulated urea production in livers from both septic and sham-operated control rats. Urea release was approximately 1.2 and 2.0 mg urea nitrogen.g-1.h-1 for 1 and 5 mM NH4Cl, respectively, and was equal for both groups. With amino acids as substrate, urea production was significantly greater in livers from septic animals compared with controls. Phenylephrine stimulated urea production in the sham-operated group by about twofold, whereas in the septic group urea release was slightly inhibited. Gluconeogenesis from lactate was inhibited by NH4Cl (1 and 5 mM) in both groups, with no difference between groups. In contrast to enhanced ureagenesis from amino acids in septic rats, gluconeogenesis was decreased by approximately 24% (P less than 0.5). Similarly, phenylephrine (1 microM) stimulated gluconeogenesis by 13 +/- 1 mumol.g-1.h-1 in sham-operated rats but only by 9 +/- 1 mumol.g-1.h-1 in septic rats (P less than 0.02). These results suggest that hepatic gluconeogenic and ureagenic pathways are intact in sepsis but that altered substrate preference and hormone sensitivity may result in decreased gluconeogenesis in the presence of elevated amino acid levels.


1959 ◽  
Vol 196 (2) ◽  
pp. 231-234 ◽  
Author(s):  
N. Altszuler ◽  
R. Steele ◽  
A. Dunn ◽  
J. S. Wall ◽  
R. C. de Bodo

The mechanism whereby growth hormone diminishes the hypoglycemic effect of insulin was investigated in hypophysectomized dogs using a C14 glucose dilution technique. An intravenous injection of insulin into the normal dog increased the rate of glucose utilization, and the resulting hypoglycemia was promptly abolished by an increased rate of glucose production. In the hypophysectomized dog prior to growth hormone administration, the insulin injection increased the rate of glucose utilization to a greater extent than in the normal animal, while the ability to increase the rate of glucose production was shown to be limited. In the hypophysectomized dog, a growth hormone regimen (1 mg/kg/day for 4 days) increased the rate of glucose production and utilization. The intravenous injection of insulin during the growth hormone regimen resulted in a lesser increase in the rate of plasma glucose utilization than observed prior to the growth hormone regimen. Furthermore, the growth hormone regimen improved the animal's limited ability to increase glucose production in response to the insulin-induced hypoglycemia. These effects of growth hormone contribute to the decreased effectiveness of insulin. The relationship of the ‘anti-insulin’ effect of growth hormone to its influence on glucose turnover is discussed.


1992 ◽  
Vol 263 (2) ◽  
pp. E400-E415 ◽  
Author(s):  
A. Mari

A simple tracer-based method for calculating the rate of appearance of endogenous substances in the non-steady state, free from the inconsistencies of Steele's equation, is still lacking. This paper presents a method based on a two-compartment model by which the rate of appearance can be calculated with only a modest increase in complexity over Steele's approach. An equation is developed where the rate of appearance is expressed as a sum of three terms: a steady-state term, a term for the first compartment, and a term for the second compartment. The formula employs three parameters and makes the relationship between rate of appearance and specific activity changes explicit. An equation is also provided for estimating the error of the method in each individual run. The algorithm can be implemented with a spreadsheet on a personal computer. Simulated and experimental data obtained by the hyperinsulinemic euglycemic glucose clamp technique were used as a test. The accuracy with which the time course of glucose production could be reconstructed was clearly better than that using Steele's equation. Marked negative values for endogenous glucose output were calculated with Steele's equation but not with the new method. The characteristics of generality, simplicity, and accuracy and the availability of an error estimate make this new method suitable for routine application to non-steady-state tracer analysis.


2000 ◽  
Vol 84 (2) ◽  
pp. 157-163 ◽  
Author(s):  
T. Obitsu ◽  
D. Bremner ◽  
E. Milne ◽  
G. E. Lobley

The effect of abomasal infusion of glucose (120 kJ/d per kg body weight (BW)0·75, 758 mmol/d) on urea production, plasma alanine-N flux rate and the conversion of alanine-N to urea was studied in sheep offered a low-N diet at limited energy intake (500 kJ/d per kg BW0·75), based on hay and grass pellets. Glucose provision reduced urinary N (P= 0·040) and urea (P= 0·009) elimination but this was offset by poorer N digestibility. Urea-N production was significantly reduced (822v. 619 mmol/d,P= 0·024) by glucose while plasma alanine-N flux rate was elevated (295v. 342 mmol/d,P= 0·011). The quantity of urea-N derived from alanine tended to be decreased by glucose (127v. 95 mmol/d) but the fraction of urea production from alanine was unaltered (15 %). Plasma urea and alanine concentrations (plus those of the branched chain amino acids) decreased in response to exogenous glucose, an effect probably related to enhanced anabolic usage of amino acids and lowered urea production.


2021 ◽  
Vol 79 (11) ◽  
pp. 1372
Author(s):  
Zhao Zhao ◽  
Shiwen Cheng ◽  
Yuezhong Mao ◽  
Jianxi Ying ◽  
Shiyi Tian ◽  
...  

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