The reliability of rates of glucose appearance in vivo calculated from single tracer injections

1979 ◽  
Vol 57 (11) ◽  
pp. 1267-1274 ◽  
Author(s):  
John R. Allsop ◽  
Robert R. Wolfe ◽  
Joseph J. DiStephano III ◽  
John F. Burke
Keyword(s):  
Plasma Glucose ◽  
Infusion Rate ◽  
Specific Radioactivity ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Constant Infusion ◽  
Glucose Turnover ◽  
Time Curve ◽  
The Mean

The rate of appearance of unlabelled glucose was calculated from changes in plasma glucose specific radioactivity after a single intravenous injection of labelled glucose and compared with the actual constant infusion rate of unlabelled glucose into an anaesthetized dog with all sources of endogenous glucose production surgically removed. The mean steady-state rate of appearance of unlabelled glucose calculated from the area under the specific radioactivity versus time curve was 7% higher than the actual infusion rate (n = 4), but the difference was not statistically significant. The variability in the rate calculated in this manner was, however, greater than the variability we have reported with rates determined from a primed constant infusion of tracer. Using 15- to 60- or 60- to 120-min specific radioactivity data the mean rate of appearance of glucose, calculated on the assumption of a one-pool model for glucose turnover in vivo, was approximately 60% higher than the actual infusion rate. The results also indicate that it is possible to construct multi-pool models, but it is difficult to equate specific physiological events with the individual terms of the multi-exponential equation which describes the changes in plasma glucose specific radioactivity.

scholarly journals Mass spectrometry-based microassay of 2H and 13C plasma glucose labeling to quantify liver metabolic fluxes in vivo

2015 ◽  
Vol 309 (2) ◽  
pp. E191-E203 ◽  
Author(s):  
Clinton M. Hasenour ◽  
Martha L. Wall ◽  
D. Emerson Ridley ◽  
Curtis C. Hughey ◽  
Freyja D. James ◽  
...  
Keyword(s):  
Steady State ◽  
Plasma Glucose ◽  
Ad Hoc ◽  
Citrate Synthase ◽  
Physiological Stress ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Hepatic Glucose

Mouse models designed to examine hepatic metabolism are critical to diabetes and obesity research. Thus, a microscale method to quantitatively assess hepatic glucose and intermediary metabolism in conscious, unrestrained mice was developed. [13C3]propionate, [2H2]water, and [6,6-2H2]glucose isotopes were delivered intravenously in short- (9 h) and long-term-fasted (19 h) C57BL/6J mice. GC-MS and mass isotopomer distribution (MID) analysis were performed on three 40-μl arterial plasma glucose samples obtained during the euglycemic isotopic steady state. Model-based regression of hepatic glucose and citric acid cycle (CAC)-related fluxes was performed using a comprehensive isotopomer model to track carbon and hydrogen atom transitions through the network and thereby simulate the MIDs of measured fragment ions. Glucose-6-phosphate production from glycogen diminished, and endogenous glucose production was exclusively gluconeogenic with prolonged fasting. Gluconeogenic flux from phospho enolpyruvate (PEP) remained stable, whereas that from glycerol modestly increased from short- to long-term fasting. CAC flux [i.e., citrate synthase ( V CS)] was reduced with long-term fasting. Interestingly, anaplerosis and cataplerosis increased with fast duration; accordingly, pyruvate carboxylation and the conversion of oxaloacetate to PEP were severalfold higher than V CS in long-term fasted mice. This method utilizes state-of-the-art in vivo methodology and comprehensive isotopomer modeling to quantify hepatic glucose and intermediary fluxes during physiological stress in mice. The small plasma requirements permit serial sampling without stress and the affirmation of steady-state glucose kinetics. Furthermore, the approach can accommodate a broad range of modeling assumptions, isotope tracers, and measurement inputs without the need to introduce ad hoc mathematical approximations.

scholarly journals Effects of Somatostatin and Glucagon on the Utilization of [2_14C] Propionate in Glucose Production in Vivo in Sheep

1980 ◽  
Vol 33 (4) ◽  
pp. 457 ◽  
Author(s):  
Ronald P Brockman ◽  
Cindy Greer
Keyword(s):  
Continuous Infusion ◽  
Plasma Glucose ◽  
Control Period ◽  
Specific Radioactivity ◽  
Glucose Production ◽  
Irreversible Loss ◽  
Selective Effect ◽  
Glycogenolytic Effect ◽  
Glucose Synthesis

This study examined the effects of hypoglucagonaemia and hyperglucagonaemia on the incorporation of 14C from [2-14C]propionate into plasma glucose of sheep in vivo. The sheep were adult ewes fed a maintenance diet of lucerne pellets delivered in equal aliquots hourly. The irreversible loss of glucose was determined by the continuous infusion of [6-3H]glucose. During the control period (the hour immediately preceding infusion of hormones) 63 �2 % of the propionate was converted to glucose, accounting for 30�2 % of glucose production. Glucagon deficiency, induced by infusion of somatostatin (100 J1g/h), did not affect gluconeogenesis and the irreversible loss of glucose significantly. However, glucagon infusion at 11 �5 �O� 6 J1g/h significantly increased the irreversible loss of glucose, with the greatest increase occurring in the first 15 min of infusion. The 14C specific radioactivity of glucose and the fraction of glucose derived from propionate decreased significantly during glucagon infusion. The data are consistent with glucagon having a marked glycogenolytic effect initially, but little or no selective effect in promoting the utilization of propionate for glucose synthesis in vivo in sheep.

scholarly journals The realiability of rates of glucose appearance in vivo calculated from constant tracer infusions

1978 ◽  
Vol 172 (3) ◽  
pp. 407-416 ◽  
Author(s):  
J R Allsop ◽  
R R Wolfe ◽  
J F Burke
Keyword(s):  
Specific Radioactivity ◽  
Glucose Production ◽  
Volume Of Distribution ◽  
Endogenous Glucose Production ◽  
Single Step ◽  
Actual Rate ◽  
Steady State Rate ◽  
Isotope Technique ◽  
State Rate

The rate of appearance of unlabelled glucose was calculated from tracer data and compared with the actual rate of infusion of unlabelled glucose into a anaesthetized dog with all sources of endogenous glucose production surgically removed. The mean steady-state rate of appearance of unlabelled glucose calculated from the equilibrium specific radioactivity was insignificantly higher (0.3%) than the actual rate of infusion of unlabelled glucose (n = 6). During non-steady states, a time-variable volume of distribution of glucose (V) was necessary to predict the rate of appearance of unlabelled glucose correctly from the pool-dependent equation described by Steele [(1959) Ann. N.Y. Acad. Sci. 82, 420–430]. Rapid fluctuations in the rate of appearance of glucose could be predicted reasonably well by using a fixed value of V for 40ml/kg, but by using larger fixed values for V (100–160ml/kg) the rates were inaccurate. The pool-dependent two-radiactive-isotope technique described by Issekutz, Issekutz & Elahi [(1974) Can. J. Physiol. Pharmacol. 52, 215–224] predicted single-step increases in the rate of infusion of glucose reasonably accurately, but the Steele (1959) equation was better at predicting sequential changes in the rate of infusion of unlabelled glucose.

scholarly journals Metabolism of glucose in hyper- and hypo-thyroid rats in vivo. Glucose-turnover values and futile-cycle activities obtained with 14C- and 3H-labelled glucose

1979 ◽  
Vol 182 (2) ◽  
pp. 565-575 ◽  
Author(s):  
F Okajima ◽  
M Ui
Keyword(s):  
Blood Glucose ◽  
Specific Radioactivity ◽  
Glucose Production ◽  
Liver Glycogen ◽  
Glucose Turnover ◽  
Futile Cycle ◽  
Futile Cycles ◽  
The Difference ◽  
Glucose Recycling

1. A trace amount of glucose labelled with 14C uniformly and with 3H at position 2, 3 or 6 was injected intravenously into starved rats to measure the turnover rate of blood glucose. 2. Reliable estimates were made based on the semilogarithmic plot of specific radioactivity of the glucose contained in whole blood samples taken from the tail vein. 3. Glucose turned over more rapidly in hyperthyroid and more slowly in hypothyroid than in euthyroid rats. The percentage contribution of glucose recycling (determined from the difference in replacement rates between [U-14C]glucose and [6-3H]glucose) to the glucose utilization increased on induction of hyperthyroidism. 4. Futile cycles between glucose and glucose 6-phosphate (determined from the difference between replacement rates of [2-3H]glucose and [6-3H]glucose) were activated and inactivated by induction of hyperthyroid and hypothyroid states respectively. 5. The hepatic content of glycogen was much lower in hyper- and hypo-thyroid than in euthyroid rats. The enhanced glucose production in hyperthyroid rats resulted from not only activationof hepatic gluconeogenesis but also diversion of the final product of gluconeogenesis from liver glycogen to blood glucose. In hypothyroidism, the inhibition of gluconeogensis led to suppression of both glucose production and glycogenesis in the liver.

Modulation of in vivo insulin action by dietary protein during pregnancy

1995 ◽  
Vol 268 (4) ◽  
pp. E722-E729 ◽  
Author(s):  
M. C. Sugden ◽  
M. J. Holness
Keyword(s):  
Dietary Protein ◽  
Infusion Rate ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Protein Diet ◽  
Nonesterified Fatty Acid ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Triacylglycerol Concentration ◽  
Protein Group

Rats were provided with a standard 20% protein diet or an isocaloric 8% protein diet from day 1 of gestation and were studied on day 19 of pregnancy. Fetal numbers per dam were unchanged, but total fetal weight at day 19 of gestation was reduced by 10% (P < 0.001) in the 8% protein group. In the basal state, endogenous glucose production (Ra) and muscle glucose uptake/phosphorylation were not significantly affected by dietary protein content. The glucose infusion rate required to maintain glycemia and Ra during euglycemic-hyperinsulinemic clamp (insulin infusion rate of 4.17 mU.kg-1.min-1) were reduced in the 8% protein group by 17% (P < 0.05) and 76% (P < 0.001), respectively. Suppression of Ra by insulin was not significant in the 20% protein group. Insulin-stimulated glucose disappearance (Rd) was 24% lower (P < 0.001) in the 8% protein group (25.0 +/- 0.8 mg.min-1.kg-1) than in the 20% protein group (32.7 +/- 0.5 mg.min-1.kg-1). The overall increment in muscle glucose utilization index (mean of 6 muscles) elicited by insulin was impaired by 38.1 +/- 4.0%. Insulin suppressed nonesterified fatty acid concentration (NEFA) by 83% (P < 0.001) and plasma triacylglycerol concentration (TAG) by 67% (P < 0.05) in the 20% protein group but evoked only a 43% (P < 0.01) decline in plasma NEFA and did not significantly suppress plasma TAG in the 8% protein group.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals The design of experiments using isotopes for the determination of the rates of disposal of blood-borne substrates in vivo with special reference to glucose, ketone bodies, free fatty acids and proteins

1973 ◽  
Vol 136 (3) ◽  
pp. 503-518 ◽  
Author(s):  
Dennis F. Heath ◽  
Roger N. Barton
Keyword(s):  
Fatty Acids ◽  
Steady State ◽  
Free Fatty Acids ◽  
Ketone Bodies ◽  
Specific Radioactivity ◽  
Constant Infusion ◽  
Time Curve ◽  
Constant Rate

1. The two well-known methods of estimating rates of irreversible disposal (R) of blood-borne substrates in vivo by isotope experiments involve estimating the specific radioactivity (S) of the substrate in blood either after single intravenous injection of labelled substrate or during its infusion at a constant rate. The value of R is calculated from the S–time curve, usually by assuming: (i) a metabolic steady state with respect to substrate, (ii) the passage of all substrate through the blood, and (iii) the absence of certain types of recycling via blood. 2. In a theoretical investigation we show how experiments can be performed and R calculated from analyses of blood when one or more of the above assumptions is unjustified, by using glucose, ketone bodies, plasma free fatty acids and proteins as examples. In general the methods require single injection procedures, with estimation of the total quantity of label in the substrate in blood and the substrate concentration instead of only S. Such values give estimates of R with standard errors even when only one blood specimen is taken from each of a group of animals, as is convenient when working with small animals or substrates in low concentration, and when the animals are in a non-steady state in which constant infusion procedures are invalid. 3. Similar methods give the fraction of label injected as one compound which passes through another (the isotopic yield). 4. The methods are not always applicable, and cannot be applied to plasma proteins in some pathological conditions. A questionnaire for assessing their applicability is given.

246-OR: Contribution of Plasma Glucose and Hormones to the Acute Compensatory Rise in Endogenous Glucose Production (EGP) during Glucosuria in T2D Patients

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 246-OR
Author(s):  
MARIAM ALATRACH ◽  
CHRISTINA AGYIN ◽  
NITCHAKARN LAICHUTHAI ◽  
JOHN M. ADAMS ◽  
MUHAMMAD ABDUL-GHANI ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Endogenous Glucose

scholarly journals Absorption and metabolism of glucose by the mesenteric-drained viscera of sheep fed on dried-grass or ground, maize-based diets

1985 ◽  
Vol 54 (2) ◽  
pp. 449-458 ◽  
Author(s):  
A. N. Janes ◽  
T. E. C. Weekes ◽  
D. G. Armstrong
Keyword(s):  
Small Intestine ◽  
Turnover Rate ◽  
Glucose Utilization ◽  
Venous Blood ◽  
Glucose Production ◽  
Glucose Absorption ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Glucose Turnover ◽  
Total Glucose

1. Sheep fitted with re-entrant canulas in the proximal duodenum and terminal ileum were used to determine the amount of α-glucoside entering, and apparently disappearing from, the small intestine when either dried-grass or ground maize-based diets were fed. The fate of any α-glucoside entering the small intestine was studied by comparing the net disappearance of such a-glucoside from the small intestine with the absorption of glucose into the mesenteric venous blood.2. Glucose absorption from the small intestine was measured in sheep equipped with catheters in the mesenteric vein and carotid artery. A continuous infusion of [6-3H]glucose was used to determine glucose utilization by the mesenteric-drained viscera and the whole-body glucose turnover rate (GTR).3. The amounts of α-glucoside entering the small intestine when the dried-grass and maize-based diets were given were 13.9 (SE 1.5) and 95.4 (SE 16.2) g/24 h respectively; apparent digestibilities of such α-glucoside in the small intestine were 60 and 90% respectively.4. The net absorption of glucose into the mesenteric venous blood was —2.03 (SE 1.20) and 19.28 (SE 0.75) mmol/h for the dried-grass and maize-based diets respectively. Similarly, total glucose absorption amounted to 1.52 (SE 1.35) and 23.33 (SE 1.86) mmol/h (equivalent to 7 and 101 g/24 h respectively). These values represented 83 and 11 1% of the a-glucoside apparently disappearing from the small intestine, determined using the re-entrant cannulated sheep.5. Total glucose absorption represented 8 and 61% of the whole-body GTR for the dried-grass and maize-based diets respectively. Endogenous glucose production was significantly lower when the sheep were fed on the maize-based diet compared with the dried-grass diet.6. The mesenteric-drained viscera metabolized a small amount of glucose, equivalent to 234 and 17% of the total glucose absorbed for the dried-grass and maize-based diets respectively.7. It is concluded that a large proportion of the starch entering the small intestine of sheep given a maize-based diet is digested and absorbed as glucose, and thus contributes to the whole-body GTR.

Glucose production, recycling, and gluconeogenesis in normals and diabetics: a mass isotopomer [U-13C]glucose study

1996 ◽  
Vol 270 (4) ◽  
pp. E709-E717 ◽  
Author(s):  
J. A. Tayek ◽  
J. Katz
Keyword(s):  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Tricarboxylic Acid Cycle ◽  
Glucose Production ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Glucose Turnover ◽  
Insulin Dependent ◽  
Gas Chromatography Mass Spectroscopy ◽  
Mass Isotopomer

Eight normal controls and nine non-insulin-dependent diabetes mellitus diabetics were, after an overnight fast, infused for 3 h with [6-3H]- and with [U-13C]glucose with six 13C carbons at rates from 0.03 to 0.15 mg.kg-1.min-1. Plasma glucose and lactate were assayed by gas chromatography-mass spectroscopy. Several parameters of glucose metabolism were calculated from the mass isotopomer distribution. Glucose production (GP) determined with [6-3H]- and [U-13C]glucose agreed closely. GP was 1.9 +/- 0.16 (range 1.3-2.5) mg.kg-1.min-1 in controls and 2.8 +/- 0.29 (1.7-4.5) mg.kg-1.min-1 in diabetics (P < 0.05). The correlation in diabetes between plasma glucose and GP (r = 0.911, P < 0.01) was close. Recycling of carbon (8 vs 7%) dilution by unlabeled carbon (2- vs 2.3-fold), and dilution via the tricarboxylic acid cycle (1.5-fold) were similar in controls and diabetics. Gluconeogenesis was 0.90 +/- 0.08 (0.5-1.3) mg.kg-1.min-1 in controls and 1.30 +/- 0.13 (0.8-1.9) mg.kg-1.min-1 in diabetics (P < 0.05). Gluconeogenesis contributions to GP were 46.6 +/- 4.0% (26-61%) in the controls and 48.8 +/- 5.7% (32-83%) in diabetics. We show that, using [U-13C]glucose infusion of 2-5% of glucose turnover (0.03-0.10 mg.kg-1.min-1), a large number of parameters of glucose metabolism may be determined in humans.

scholarly journals Growth hormone signaling and action in obese versus lean human subjects

2019 ◽  
Vol 316 (2) ◽  
pp. E333-E344 ◽  
Author(s):  
Morten Lyng Høgild ◽  
Ann Mosegaard Bak ◽  
Steen Bønløkke Pedersen ◽  
Jørgen Rungby ◽  
Jan Frystyk ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Growth Hormone ◽  
Human Subjects ◽  
Glucose Production ◽  
Relative Increase ◽  
Antagonistic Effect ◽  
Endogenous Glucose Production ◽  
Metabolic Adaptation ◽  
Igf I

Growth hormone (GH) levels are blunted in obesity, but it is not known whether this relates to altered GH sensitivity and whether this influences the metabolic adaptation to fasting. Therefore, we investigated the effect of obesity on GH signal transduction and fasting-induced changes in GH action. Nine obese (BMI 35.7 kg/m2) and nine lean (BMI 21.5 kg/m2) men were studied in a randomized crossover design with 1) an intravenous GH bolus, 2) an intravenous saline bolus, and 3) 72 h of fasting. Insulin sensitivity (hyperinsulinemic, euglycemic clamp) and substrate metabolism (glucose tracer and indirect calorimetry) were measured in studies 1 and 2. In vivo GH signaling was assessed in muscle and fat biopsies. GH pharmacokinetics did not differ between obese and lean subjects, but endogenous GH levels were reduced in obesity. GH signaling (STAT5b phosphorylation and CISH mRNA transcription), and GH action (induction of lipolysis and peripheral insulin resistance) were similar in the two groups, but a GH-induced insulin antagonistic effect on endogenous glucose production only occurred in the obese. Fasting-induced IGF-I reduction was completely abrogated in obese subjects despite a comparable relative increase in GH levels (ΔIGF-I: lean, −66 ± 10 vs. obese, 27 ± 16 µg/l; P < 0.01; ΔGH: lean, 647 ± 280 vs. obese, 544 ± 220%; P = 0.76]. We conclude that 1) GH signaling is normal in obesity, 2) in the obese state, the preservation of IGF-I with fasting and the augmented GH-induced central insulin resistance indicate increased hepatic GH sensitivity, 3) blunted GH levels in obesity may protect against insulin resistance without compromising IGF-I status.

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