scholarly journals Contributions of net hepatic glycogenolysis and gluconeogenesis to glucose production in cirrhosis

1999 ◽  
Vol 276 (3) ◽  
pp. E529-E535 ◽  
Author(s):  
Kitt Falk Petersen ◽  
Martin Krssak ◽  
Victor Navarro ◽  
Visvanathan Chandramouli ◽  
Ripudaman Hundal ◽  
...  

Net hepatic glycogenolysis and gluconeogenesis were examined in normal ( n = 4) and cirrhotic ( n = 8) subjects using two independent methods [13C nuclear magnetic resonance spectroscopy (NMR) and a2H2O method]. Rates of net hepatic glycogenolysis were calculated by the change in hepatic glycogen content before (∼11:00 PM) and after (∼7:00 AM) an overnight fast using13C NMR and magnetic resonance imaging. Gluconeogenesis was calculated as the difference between the rates of glucose production determined with an infusion of [6,6-2H2]glucose and net hepatic glycogenolysis. In addition, the contribution of gluconeogenesis to glucose production was determined by the2H enrichment in C-5/C-2 of blood glucose after intake of2H2O (5 ml/kg body water). Plasma levels of total and free insulin-like growth factor I (IGF-I) and IGF-I binding proteins-1 and -3 were significantly decreased in the cirrhotic subjects ( P < 0.01 vs. controls). Postprandial hepatic glycogen concentrations were 34% lower in the cirrhotic subjects ( P = 0.007). Rates of glucose production were similar between the cirrhotic and healthy subjects [9.0 ± 0.9 and 10.0 ± 0.8 μmol ⋅ kg body wt−1 ⋅ min−1, respectively]. Net hepatic glycogenolysis was 3.5-fold lower in the cirrhotic subjects ( P = 0.01) and accounted for only 13 ± 6% of glucose production compared with 40 ± 10% ( P = 0.03) in the control subjects. Gluconeogenesis was markedly increased in the cirrhotic subjects and accounted for 87 ± 6% of glucose production vs. controls: 60 ± 10% ( P = 0.03). Gluconeogenesis in the cirrhotic subjects, as determined from the2H enrichment in glucose C-5/C-2, was also increased and accounted for 68 ± 3% of glucose production compared with 54 ± 2% ( P = 0.02) in the control subjects. In conclusion, cirrhotic subjects have increased rates of gluconeogenesis and decreased rates of net hepatic glycogenolysis compared with control subjects. These alterations are likely important contributing factors to their altered carbohydrate metabolism.

1996 ◽  
Vol 270 (1) ◽  
pp. E186-E191 ◽  
Author(s):  
K. F. Petersen ◽  
T. Price ◽  
G. W. Cline ◽  
D. L. Rothman ◽  
G. I. Shulman

Relative contributions of net hepatic glycogenolysis and gluconeogenesis to glucose production during the first 12 h of a fast were studied in 13 healthy volunteers by noninvasively measuring hepatic glycogen content using 13C nuclear magnetic resonance spectroscopy. Rates of net hepatic glycogenolysis were calculated by multiplying the change in liver glycogen content with liver volume determined by magnetic resonance imaging. Rates of gluconeogenesis were calculated as the difference between rates of glucose production determined with an infusion of [6,6-2H]-glucose and net hepatic glycogenolysis. At 6 P.M. a liquid mixed meal (1,000 kcal; 60% as glucose) was given, to which [2-2H]glucose was added to trace glucose absorption. Hepatic glycogen content was measured between 11 P.M. and 1 A.M. and between 3 and 6 A.M. At 11 P.M. the concentration was 470 mM and it decreased linearly during the night. The mean liver volume was 1.47 +/- 0.06 liters. Net hepatic glycogenolysis (5.8 +/- 0.8 mumol.kg body wt-1.min-1) accounted for, on average, 45 +/- 6% and gluconeogenesis for 55 +/- 6% of the rate of whole body glucose production (12.6 +/- 0.6 mumol.kg body wt-1.min-1). In conclusion, this study shows that, even early in the phase of the postabsorptive period when liver glycogen stores are maximal, gluconeogenesis contributes approximately 50% to hepatic glucose production.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Chuanjiang Li ◽  
Hui Wang ◽  
Manuel Juárez ◽  
Eric Dongliang Ruan

Maillard reaction is a nonenzymatic reaction between reducing sugars and free amino acid moieties, which is known as one of the most important modifications in food science. It is essential to characterize the structure of Amadori rearrangement products (ARPs) formed in the early stage of Maillard reaction. In the present study, the Nα-acetyl-lysine-glucose model had been successfully set up to produce ARP, Nα-acetyl-lysine-glucose. After HPLC purification, ARP had been identified by ESI-MS with intense [M+H]+ ion at 351 m/z and the purity of ARP was confirmed to be over 90% by the relative intensity of [M+H]+ ion. Further structural characterization of the ARP was accomplished by using nuclear magnetic resonance (NMR) spectroscopy, including 1D 1H NMR and 13C NMR, the distortionless enhancement by polarization transfer (DEPT-135) and 2D 1H-1H and 13C-1H correlation spectroscopy (COSY) and 2D nuclear overhauser enhancement spectroscopy (NOESY). The complexity of 1D 1H NMR and 13C NMR was observed due to the presence of isomers in glucose moiety of ARP. However, DEPT-135 and 2D NMR techniques provided more structural information to assign the 1H and 13C resonances of ARP. 2D NOESY had successfully confirmed the glycosylated site between 10-N in Nα-acetyl-lysine and 7′-C in glucose.


2002 ◽  
Vol 282 (6) ◽  
pp. E1360-E1368 ◽  
Author(s):  
Thongchai Pratipanawatr ◽  
Wilailak Pratipanawatr ◽  
Clifford Rosen ◽  
Rachele Berria ◽  
Mandeep Bajaj ◽  
...  

The effects of insulin-like growth factor I (IGF-I) and insulin on free fatty acid (FFA) and glucose metabolism were compared in eight control and eight type 2 diabetic subjects, who received a two-step euglycemic hyperinsulinemic (0.25 and 0.5 mU · kg−1 · min−1) clamp and a two-step euglycemic IGF-I (26 and 52 pmol · kg−1 · min−1) clamp with [3-3H]glucose, [1-14C]palmitate, and indirect calorimetry. The insulin and IGF-I infusion rates were chosen to augment glucose disposal (Rd) to a similar extent in control subjects. In type 2 diabetic subjects, stimulation of Rd (second clamp step) in response to both insulin and IGF-I was reduced by ∼40–50% compared with control subjects. In control subjects, insulin was more effective than IGF-I in suppressing endogenous glucose production (EGP) during both clamp steps. In type 2 diabetic subjects, insulin-mediated suppression of EGP was impaired, whereas EGP suppression by IGF-I was similar to that of controls. In both control and diabetic subjects, IGF-I-mediated suppression of plasma FFA concentration and inhibition of FFA turnover were markedly impaired compared with insulin ( P < 0.01–0.001). During the second IGF-I clamp step, suppression of plasma FFA concentration and FFA turnover was impaired in diabetic vs. control subjects ( P < 0.05–0.01). Conclusions: 1) IGF-I is less effective than insulin in suppressing EGP and FFA turnover; 2) insulin-resistant type 2 diabetic subjects also exhibit IGF-I resistance in skeletal muscle. However, suppression of EGP by IGF-I is not impaired in diabetic individuals, indicating normal hepatic sensitivity to IGF-I.


1977 ◽  
Vol 55 (12) ◽  
pp. 2297-2301 ◽  
Author(s):  
Ulf Berg

The interpretation of the temperature dependent nmr spectra of the three thiobenzmorpholides 1–3 in terms of torsional libration proposed in the title article is criticized. Pure samples of cis-1 and trans-1 have been prepared and studied by dynamic 1H and 13C nmr. A new interpretation is presented which involves the freezing of the passage over the steric barrier with a planar Ph—C(S)N transition state.


1977 ◽  
Vol 55 (9) ◽  
pp. 1575-1582 ◽  
Author(s):  
James S. Craigie ◽  
A. Gavin McInnes ◽  
Mark A. Ragan ◽  
John A. Walter

Alcoholic extracts of Fucus vesiculosus contain small quantities of low molecular weight polyphenols derived from phloroglucinol and 2,2′,4,4′,6,6′-hexahydroxybiphenyl. 1H and 13C nmr were used to identify two of these as 4-(2′′,4′′,6′′-trihydroxyphenoxy)-2,2′,4′,6,6′-pentahydroxybiphenyl and 4-(2′′-(2′′′,4′′′,6′′′-trihydroxyphenoxy)-4′′,6′′-dihydroxyphenoxy)-2,2′,4′, 6,6′-pentanydroxybiphenyl.


1980 ◽  
Vol 58 (17) ◽  
pp. 1839-1846 ◽  
Author(s):  
Gerardo Burton ◽  
Robert L. Baxter ◽  
J. Martyn Gunn ◽  
Philip J. Sidebottom ◽  
Paul E. Fagerness ◽  
...  

Applications of 13C nmr in following the metabolism and fate of 13C enriched substrates in whole cells are described. Studies on the elaboration of coproporphyrinogens I (2a) and III (2b) from [5-13C]-δ-aminolevulinic acid (1) and [11-13C-porphobilinogen (PBG, 3), in Rhodopseudomonasspheroides and Propionibacteriumshermanii, respectively, the randomization of 13C from [3-13C]-propionate by P. shermanii, the biosynthesis of citrate, gentisalcohol (4), and patulin (5) from [2-13C]-acetate by Penicilliumurticae, and the anaerobic metabolism of [1-13C]-glucose in rabbit erythrocytes are reported.


2002 ◽  
Vol 92 (1) ◽  
pp. 188-194 ◽  
Author(s):  
Victoria Matas Bonjorn ◽  
Martin G. Latour ◽  
Patrice Bélanger ◽  
Jean-Marc Lavoie

The purpose of the present study was to test the hypothesis that a prior period of exercise is associated with an increase in hepatic glucagon sensitivity. Hepatic glucose production (HGP) was measured in four groups of anesthetized rats infused with glucagon (2 μg · kg−1 · min−1 iv) over a period of 60 min. Among these groups, two were normally fed and, therefore, had a normal level of liver glycogen (NG). One of these two groups was killed at rest (NG-Re) and the other after a period of exercise (NG-Ex; 60 min of running, 15–26 m/min, 0% grade). The two other groups of rats had a high hepatic glycogen level (HG), which had been increased by a fast-refed diet, and were also killed either at rest (HG-Re) or after exercise (HG-Ex). Plasma glucagon and insulin levels were increased similarly in all four conditions. Glucagon-induced hyperglycemia was higher ( P < 0.01) in the HG-Re group than in all other groups. HGP in the HG-Re group was not, however, on the whole more elevated than in the NG-Re group. Exercised rats (NG-Ex and HG-Ex) had higher hyperglycemia, HGP, and glucose utilization than rested rats in the first 10 min of the glucagon infusion. HG-Ex group had the highest HGP throughout the 60-min experiment. It is concluded that hyperglucagonemia-induced HGP is stimulated by a prior period of exercise, suggesting an increased sensitivity of the liver to glucagon during exercise.


2020 ◽  
Vol 4 (3) ◽  
pp. 425-433
Author(s):  
Stefan Stender ◽  
Vlad G. Zaha ◽  
Craig R. Malloy ◽  
Jessica Sudderth ◽  
Ralph J. DeBerardinis ◽  
...  

1998 ◽  
Vol 274 (1) ◽  
pp. E65-E71 ◽  
Author(s):  
Ekkehard Küstermann ◽  
Joachim Seelig ◽  
Basil Künnecke

The first in vivo detection of a vitamin with nuclear magnetic resonance (NMR) is reported for mammalian liver. Vitamin C, also known as ascorbic acid, was monitored noninvasively in rat liver by “whole body”13C NMR spectroscopy at high field after infusion of [1,2-13C2]glucose into anesthetized rats. Generally, the carbon resonances of ascorbic acid overlap with those of other highly abundant cellular metabolites, thus precluding their observation in situ. This problem was resolved by taking advantage of the13C-13C spin couplings introduced by the two covalently bound13C nuclei in [1,2-13C2]glucose. During glucose metabolism, [5,6-13C2]ascorbic acid was synthesized, which also exhibited characteristic13C homonuclear spin couplings. This feature enabled the spectral discrimination of ascorbic acid from overlapping singlet resonances of other metabolites. Quantitative analysis of the spin-coupling patterns provided an estimate of the turnover rate of hepatic ascorbic acid in vivo (1.9 ± 0.4 nmol ⋅ min−1 ⋅ g−1) and a novel approach toward a better understanding of optimal ascorbic acid requirements in humans. The results obtained in vivo were confirmed with high-resolution proton and13C NMR spectroscopy of liver extracts.


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