Limitations in estimating gluconeogenesis and Cori cycling from mass isotopomer distributions using [U-13C6]glucose

1998 ◽  
Vol 274 (5) ◽  
pp. E954-E961 ◽  
Author(s):  
Bernard R. Landau ◽  
John Wahren ◽  
Karin Ekberg ◽  
Stephen F. Previs ◽  
Dawei Yang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Blood Glucose ◽  
Isotopic Exchange ◽  
Glucose Production ◽  
Normal Subjects ◽  
Glucose Infusion ◽  
Arterial Lactate ◽  
Overnight Fasting ◽  
Mass Isotopomer

Tayek and Katz proposed calculating gluconeogenesis’s contributions to glucose production and Cori cycling from mass isotopomer distributions in blood glucose and lactate during [U-13C6]glucose infusion [Tayek, J. A., and J. Katz. Am. J. Physiol. 272 ( Endocrinol. Metab. 35): E476–E484, 1997]. However, isotopic exchange was not adequately differentiated from dilution, nor was condensation of labeled with unlabeled triose phosphates properly equated. We introduce and apply corrected equations to data from subjects fasted for 12 and 60 h. Impossibly low contributions of gluconeogenesis to glucose production at 60 h are obtained (23–41%). Distributions in overnight-fasted normal subjects calculate to only ∼18%. Cori cycling estimates are ∼10–15% after overnight fasting and 20% after 60 h of fasting. There are several possible reasons for the underestimates. The contribution of gluconeogenesis is underestimated because glucose production from glycerol and amino acids not metabolized via pyruvate is ascribed to glycogenolysis. Labeled oxaloacetate and α-ketoglutarate can exchange during equilibrium with circulating unlabeled aspartate, glutamate, and glutamine. Also, the assumption that isotopomer distributions in arterial lactate and hepatic pyruvate are the same may not be fulfilled.

Quantifying gluconeogenesis during fasting

1997 ◽  
Vol 273 (6) ◽  
pp. E1209-E1215 ◽  
Author(s):  
Visvanathan Chandramouli ◽  
Karin Ekberg ◽  
William C. Schumann ◽  
Satish C. Kalhan ◽  
John Wahren ◽  
...  
Keyword(s):  
Steady State ◽  
Blood Glucose ◽  
Healthy Subjects ◽  
Glucose Production ◽  
Body Water ◽  
Glucose Infusion ◽  
Apparent Change ◽  
State 1

The use of2H2O in estimating gluconeogenesis’ contribution to glucose production (%GNG) was examined during progressive fasting in three groups of healthy subjects. One group ( n = 3) ingested2H2O to a body water enrichment of ≈0.35% 5 h into the fast. %GNG was determined at 2-h intervals from the ratio of the enrichments of the hydrogens at C-5 and C-2 of blood glucose, assayed in hexamethylenetetramine. %GNG increased from 40 ± 8% at 10 h to 93 ± 6% at 42 h. Another group ingested2H2O over 2.25 h, beginning at 11 h ( n = 7) and 19 h ( n = 7) to achieve ≈0.5% water enrichment. Enrichment in plasma water and at C-2 reached steady state ≈1 h after completion of2H2O ingestion. The C-5-to-C-2 ratio reached steady state by the completion of 2H2O ingestion. %GNG was 54 ± 2% at 14 h and 64 ± 2% at 22 h. A 3-h [6,6-2H2]glucose infusion was also begun to estimate glucose production from enrichments at C-6, again in hexamethylenetetramine. Glucose produced by gluconeogenesis was 0.99 ± 0.06 mg ⋅ kg−1 ⋅ min−1at both 14 and 22 h. In a third group ( n = 3) %GNG reached steady state ≈2 h after2H2O ingestion to only ≈0.25% enrichment. In conclusion, %GNG by 2 h after2H2O ingestion and glucose production using [6,6-2H2]glucose infusion, begun together, can be determined from hydrogen enrichments at blood glucose C-2, C-5, and C-6. %GNG increases gradually from the postabsorptive state to 42 h of fasting, without apparent change in the quantity of glucose produced by gluconeogenesis at 14 and 22 h.

Gluconeogenesis and the Cori cycle in 12-, 20-, and 40-h-fasted humans

1998 ◽  
Vol 275 (3) ◽  
pp. E537-E542 ◽  
Author(s):  
Joseph Katz ◽  
John A. Tayek
Keyword(s):  
Blood Glucose ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Glucose Production ◽  
Plasma Glucose Concentration ◽  
Prolonged Fasting ◽  
Cori Cycle ◽  
Isotopomer Analysis ◽  
Mass Isotopomer

Six subjects were infused with [U-13C]glucose (0.03–0.05 mg ⋅ kg−1 ⋅ min−1) starting 8–9 h after a meal, and the production of glucose, the recycling of glucose (the Cori cycle), the dilution of glucose by unlabeled carbon into the hepatic lactate-pyruvate pool, and gluconeogenesis were determined in these fasted volunteers by use of mass isotopomer analysis and equations previously described [J. A. Tayek and J. Katz. Am. J. Physiol.272 ( Endocrinol. Metab. 35): E476–E484, 1997]. A primed continuous 11-h infusion was started at 6:00 AM, and the above parameters were calculated after 3 h (for the 12-h fast) and at the end of the infusion (for the 20-h fast). Another group of five subjects was fasted for 40 h, and the above parameters were calculated as before. At 12, 20, and 40 h of fasting, respectively, blood glucose was 93 ± 2, 83 ± 2, and 71 ± 2 (SE) mg/dl; glucose production was 2.3, 1.8, and 1.77 mg ⋅ kg−1 ⋅ min−1; the recycling of labeled carbon was 8, 15, and 15%, and that of glucose molecules (Cori cycle) was 18, 35, and 36%; the contribution of gluconeogenesis to glucose production was 41, 71, and 92% or 0.96, 1.29, and 1.64 mg ⋅ kg−1 ⋅ min−1; and the contribution of other sources to glucose production was 1.37, 0.53, and 0.15 mg ⋅ kg−1 ⋅ min−1. The recycling of glucose is important in prolonged fasting for the maintenance of plasma glucose concentration. We demonstrate here that gluconeogenesis can be easily measured and that it accounts for ∼90% of glucose production after a 40-h fast.

Pulsatile hyperglucagonemia fails to increase hepatic glucose production in normal man

1987 ◽  
Vol 252 (1) ◽  
pp. E1-E7 ◽  
Author(s):  
G. Paolisso ◽  
A. J. Scheen ◽  
A. S. Luyckx ◽  
P. J. Lefebvre
Keyword(s):  
Blood Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Infusion ◽  
Metabolic Effects ◽  
Glucose Turnover ◽  
Continuous Administration ◽  
Hepatic Glucose ◽  
Normal Man

To study the metabolic effects of pulsatile glucagon administration, six male volunteers were submitted to a 260-min glucose-controlled glucose intravenous infusion using the Biostator. The endogenous secretion of the pancreatic hormones was inhibited by somatostatin (100 micrograms X h-1), basal insulin secretion was replaced by a continuous insulin infusion (0.2 mU X kg-1 X min-1), and glucagon was infused intravenously in two conditions at random: either continuously (125 ng X min-1) or intermittently (812.5 ng X min-1, with a switching on/off length of 2/11 min). Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classical methodology using a D-[3-3H]glucose infusion allowed us to study glucose turnover. While basal plasma glucagon levels were similar in both conditions (122 +/- 31 vs. 115 +/- 18 pg X ml-1), they plateaued at 189 +/- 38 pg X ml-1 during continuous infusion and varied between 95 and 501 pg X ml-1 during pulsatile infusion. When compared with continuous administration, pulsatile glucagon infusion initially induced a similar increase in endogenous (hepatic) glucose production and blood glucose, did not prevent the so-called “evanescent” effect of glucagon on blood glucose, and after 3 h tended to reduce rather than increase hepatic glucose production. In conclusion, in vivo pulsatile hyperglucagonemia in normal man fails to increase hepatic glucose production.

Effects of cold exposure and time relative to feeding on glucose metabolism of sheep using a glucose clamp approach

2003 ◽  
Vol 140 (3) ◽  
pp. 335-341 ◽  
Author(s):  
A. TAKEBAYASHI ◽  
H. SANO ◽  
T. FUJITA ◽  
K. AMBO
Keyword(s):  
Blood Glucose ◽  
Glucose Metabolism ◽  
Cold Exposure ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Glucose Clamp ◽  
Glucose Infusion ◽  
Isotope Dilution Method ◽  
Glucose Turnover ◽  
Dilution Method

An experiment combining a hyperinsulinaemic euglycaemic clamp approach and an isotope dilution method determined the effects of cold exposure and time relative to feeding on blood glucose metabolism in four sheep. The sheep, fed 20 g/kg body-weight (BW) of lucerne hay cubes and 5 g/kg BW of maize-based concentrates once daily, were exposed in turn to a thermoneutral environment (20 °C) and a cold environment (0 °C) for 20 days. The combined experiments were performed at four different times relative to feeding, i.e. 3 to 2 h, 2 to 1 h and 1 to 0 h before, and 1 to 2 h after the initiation of feeding for the basal periods, and 1 to 0 h before, and 0 to 1 h, 1 to 2 h and 3 to 4 h after the initiation of feeding for the glucose clamp periods in both environments. [U-13C]Glucose was continuously infused for 6 h after a priming injection. Insulin was continuously infused at 6·0 mU/kg BW per min for 2 h, which corresponded to the last 2 h of the [U-13C]glucose infusion. Blood glucose concentrations were maintained euglycaemic during the insulin infusion by concomitant variable glucose infusion. Blood glucose turnover rate (GTR) during the basal period was enhanced by cold exposure (P=0·01) and feeding (P=0·04). Blood GTR increased (P<0·01) with the glucose clamp. During the glucose clamp, blood GTR and glucose infusion rate (GIR) were greater (P=0·003 and P=0·001, respectively) during cold exposure than in the thermoneutral environment. Time relative to feeding influenced (P=0·003) the GIR, whereas changes in blood GTR and endogenous glucose production rate were not significant. No significant cold×feeding interaction was observed in these variables. It was suggested that, in sheep, glucose metabolism was enhanced by cold exposure and the glucose clamp. It was probable that blood glucose metabolism during the glucose clamp was influenced by cold exposure and feeding, but the combined effect of cold exposure and feeding was not significant.

A limitation in the use of mass isotopomer distributions to measure gluconeogenesis in fasting humans

1995 ◽  
Vol 269 (1) ◽  
pp. E18-E26 ◽  
Author(s):  
B. R. Landau ◽  
C. A. Fernandez ◽  
S. F. Previs ◽  
K. Ekberg ◽  
V. Chandramouli ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Glucuronic Acid ◽  
Glucose Production ◽  
Normal Subjects ◽  
Cellular Heterogeneity ◽  
Liver Lobule ◽  
Precursor Pool ◽  
Acetaminophen Glucuronide ◽  
Glucose Formation ◽  
Mass Isotopomer

The use of distributions of mass isotopomers in glucose from [U-13C]glycerol to estimate fractional rates of gluconeogenesis was examined. [U-13C]glycerol was infused into normal subjects who ingested acetaminophen and fasted for 60 h. Isotopomer distributions were measured by mass spectrometry in blood glucose and in glucuronic acid from urinary acetaminophen glucuronide. The distributions are incompatible with glucose production solely via gluconeogenesis from a single pool of triose phosphates. Rather, with the assumption of a single enriched triose phosphate pool, the distributions indicate, despite the 60 h of fasting, about as much glucose formation from an unlabeled glucose source as from that pool. Therefore the data indicate cellular heterogeneity in glycerol's metabolism, so that two or more pools with significantly different enrichments were the source of the glucose and glucuronic acid. This heterogeneity is related to much greater concentrations of glycerol in periportal than in pericentral zones of the liver lobule. Beyond evidence for heterogeneity, the findings emphasize a limitation in applying analyses of mass isotopomer distributions to measure polymer biosynthesis in the presence of heterogeneity in the precursor pool.

LEVELS OF FREE PLASMA AMINO ACIDS UNDER ACUTE NORMOBARIC HYPOXIA IN VOLUNTEERS IN FASTED AND POSTPRANDIAL STATES

2020 ◽  
pp. 108-117
Author(s):  
A.A. Chernykh ◽  
N.N. Potolitsyna ◽  
E.A. Burykh ◽  
E.R. Boyko
Keyword(s):  
Amino Acids ◽  
Normobaric Hypoxia ◽  
Adaptation To Hypoxia ◽  
Plasma Amino Acids ◽  
Fed State ◽  
Metabolic Substrates ◽  
Overnight Fasting ◽  
Group 2 ◽  
Free Plasma ◽  
Group 1

The aim of the study was to assess the effect of acute normobaric hypoxia on free plasma amino acids (AA) in volunteers after overnight fasting and in the fed state. Materials and Methods. Group 1 (n=13, aged 22–32) participated in the study in the morning after overnight fasting. Group 2 (n=9, aged 22–32) took part in the study after a light fat-free breakfast. Acute normobaric hypoxia was achieved by breathing a hypoxic gas mixture (9 % O2 and 91 % N2) through a mask. According to the experimental protocol, blood sampling from the cubital vein was performed for analysis. Free plasma amino acids were analyzed using the Aracus amino acid analyzer. Results. Prior to the hypoxia onset, at the 5th and 20th minutes of hypoxia, no statistically significant differences in free AA levels were observed in the groups (p>0.05). At the 10th minute of hypoxia the levels of four AAs (serine, threonine, glutamine, and histidine) were significantly higher in Group 1 than in Group 2 (p<0.05). This was probably due to differences in functioning of several key “harmonizing” AA transporters (ASCT1 (SLC1A4), ASCT2 (SLC1A5) and LAT1 (SC7A5)), for which the AAs were metabolic substrates. It can be assumed, that such changes were caused by currently unclear mechanisms of fast regulation of AA transporter activity, associated with nutritional status. Conclusion. We believe that our findings may be important for providing better adaptation to hypoxia, and for more efficient correction of hypoxic negative effects. Keywords: acute normobaric hypoxia, free plasma amino acids, human. Цель исследования: изучить воздействие острой нормобарической гипоксии на метаболизм свободных аминокислот (АК) плазмы крови у добровольцев, участвовавших в исследовании натощак и после лёгкого завтрака. Материалы и методы. Первая группа добровольцев (22–32 года, n=13) участвовала в исследовании утром натощак, вторая группа (22–32 года, n=9) – через 2–3 ч после лёгкого безжирового завтрака. Гипоксия создавалась путём подачи через маску дыхательной смеси, содержащей 9 % О2 и 91 % N2. В соответствии с протоколом проводился периодический забор крови из локтевой вены для анализа. Оценка уровней свободных АК плазмы крови производилась с помощью аминокислотного анализатора Aracus. Результаты. До начала гипоксии, на 5-й и 20-й мин гипоксии уровни свободных АК в первой и второй группах значимо не различались (p>0,05). На 10-й мин гипоксии между первой и второй группами наблюдались статистически значимые различия уровней четырёх АК: глутамина, серина, треонина и гистидина (p<0,05). Это, вероятно, было обусловлено изменениями в работе «гармонизирующих» мембранных транспортёров (ASCT1 (SLC1A4), ASCT2 (SLC1A5) и LAT1 (SC7A5)), для которых эти АК являются обменными субстратами. Можно предположить, что данные изменения были опосредованы пока неясными механизмами быстрой регуляции активности этих транспортёров, зависящими от питания. Выводы. Мы полагаем, что полученные результаты могут иметь значение для обеспечения адаптации организма человека к острой гипоксии и эффективной коррекции последствий гипоксического воздействия. Ключевые слова: острая нормобарическая гипоксия, свободные аминокислоты плазмы крови, человек.

Biochemische Aspekte des Aminosäuren-Stoffwechsels bei Psoriasis vulgaris / Biochemical Aspects of Amino Acid Metabolism in Psoriasis vulgaris

1973 ◽  
Vol 28 (7-8) ◽  
pp. 449-451 ◽  
Author(s):  
G. Peter ◽  
H. Angst ◽  
U. Koch
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Free Amino Acids ◽  
Free Amino ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Psoriasis Vulgaris ◽  
Normal Subjects ◽  
Pathological Process

Free and protein-bound amino acids in serum and scales were investigated. In serum the bound amino acids of psoriatics are significantly higher with exception of Pro, Met, Tyr and Phe in contrast to normal subjects. For free amino acids the differences between normal subjects and psoriatics found in serum and scales are not significant. Results are discussed in relation to the single amino acids and the biochemical correlations are outlined which takes the pathological process as a basis.

Glucose and Adenosine Triphosphate Level in Normal Subjects

1974 ◽  
Vol 125 (588) ◽  
pp. 459-460 ◽  
Author(s):  
J. Damas Mora ◽  
D. Vlissides ◽  
F. A. Jenner
Keyword(s):  
Blood Glucose ◽  
Correlation Coefficient ◽  
Adenosine Triphosphate ◽  
Whole Blood ◽  
Normal Subjects ◽  
Red Cell ◽  
Linus Pauling

In Orthomolecular Psychiatry; Treatment of Schizophrenia, edited by David Hawkins and Linus Pauling (1973), Beebe and Wendel (pp. 278–302) report a high correlation coefficient of r = 0.99 (which we calculate gives N = 42, p very much lower than 0.001) between whole blood glucose and adenosine triphosphate (ATP). This relationship they claim is no longer maintained in schizophrenics with anxiety, r = 0.16 (N = 62, p > 0.1). Erban and Hanzlicek (1966), Hansen (1972) and Hansen and Dimitrakoudi (1974) have suggested a possible significance of whole blood ATP in psychoses, and Naylor, Dick, Dick, Le Poidevin and Whyte (1973) have implicated red cell Na/K ATPases. The mechanisms involved in controlling blood ATP seemed therefore worthy of study especially if they are so dependent on glucose.

Sign in / Sign up

Export Citation Format

Share Document