Measurement of Hemoglobin Synthesis Rate in Vivo Using a Stable Isotope Method

Hibbert, Jacqueline M.; Sutherland, George; Wright, Luther L.; Wolfe, Luke; Wolfe, Kimberly A.; Gao, Shi; Gore, Dennis C.; Abd‐Elfattah, Anwar S.

doi:10.1006/abio.2001.4997

Cited by 3 publications

(8 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We first confirmed a dose and dosing schedule for 15 N-or 13 C-glycine based on previous experience [21,32,33]. In the first subject, there was significant enrichment of %APE for both 15 N and 13 C after simultaneous oral ingestion of equal amounts of 15 N-glycine and 13 Cglycine (2 g divided into 3 hourly doses), with no apparent advantage for the more expensive 13 C-glycine.…”

Section: Dose and Dosing Schedulementioning

confidence: 58%

“…Examples of this approach include the standard radioactive clinical label, 51 Cr [19], and the more precise research label, biotin [20]. In contrast, the use of a metabolic precursor that can be administered orally and biosynthetically incorporated into heme results in a cohort label [21]. Since no ex vivo labeling is required, there are no associated laboratory costs for labeling, no possibility of error in the identification of material for re-infusion, and no potential for bacterial contamination.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Use of an oral stable isotope label to confirm variation in red blood cell mean age that influences HbA1c interpretation

et al. 2014

Self Cite

View full text Add to dashboard Cite

HbA1c is commonly used to monitor glycemic control. However, there is growing evidence that the relationship between HbA1c and mean blood glucose (MBG) is influenced by variation in red blood cell (RBC) lifespan in hematologically normal individuals. Correction of HbA1c for mean RBC age (MRBC) requires a noninvasive, accurate, and affordable method to measure RBC survival. In this study, we evaluated whether a stable isotope approach would satisfy these requirements. RBC lifespan and MRBC were determined in a group of nine hematologically normal diabetic and nondiabetic subjects using oral 15N-glycine to label heme in an age cohort of RBC. The MRBC was 58.7 ± 9.1 (2SD) days and RBC lifespan was 106 ± 21 (2SD) days. This degree of variation (±15 - 20%) is consistent with previous studies using other techniques. In a subset of seven subjects, MRBC determined with the biotin label technique were available from approximately five years prior, and strongly correlated with the stable isotope values (R2 = 0.79). This study suggests that the MRBC is stable over time but varies substantially among individuals, and supports the importance of its variation in HbA1c interpretation. The characteristics of the stable isotope method support its suitability for studies to directly evaluate the impact of variation in MRBC on the interpretation of HbA1c.

show abstract

Section: Dose and Dosing Schedulementioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Use of an oral stable isotope label to confirm variation in red blood cell mean age that influences HbA1c interpretation

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…Thus, in a fasting state condition, it is difficult to hypothesize different distributions of natural isotopic enrichments of precursors in separate cell types. Moreover, background glycine isotopic enrichments in circulating erythrocytes were previously demonstrated, in animals, to approximate enrichments measured in other tissues (bone marrow) (Hibbert et al 2001). Moreover, the use of background enrichment of blood protein to assess muscle protein turnover has been directly validated in humans (Heys et al 1990).…”

Section: Methodsmentioning

confidence: 84%

Effects of inactivity on human muscle glutathione synthesis by a double-tracer and single-biopsy approach

Agostini

Libera

Rittweger

et al. 2010

The Journal of Physiology

View full text Add to dashboard Cite

Oxidative stress is often associated to inactivity-mediated skeletal muscle atrophy. Glutathione is one of the major antioxidant systems stimulated, both at muscular and systemic level, by activation of oxidative processes. We measured changes in glutathione availability, oxidative stress induction and the extent of atrophy mediated by 35 days of experimental bed rest in vastus lateralis muscle of healthy human volunteers. To assess muscle glutathione synthesis, we applied a novel single-biopsy and double-tracer ( Muscle glutathione absolute synthesis rate increased following bed rest from 5.5 ± 1.1 to 11.0 ± 1.5 mmol (kg wet tissue) −1 day −1 (mean ± s.e.m.; n = 9; P = 0.02) while glutathione concentration failed to change significantly. Bed rest induced vastus lateralis muscle atrophy, as assessed by pennation angle changes measured by ultrasonography (from 18.6 ± 1.0 to 15.3 ± 0.9 deg; P = 0.01) and thickness changes (from 2.3 ± 0.2 to 1.9 ± 0.1 cm; P < 0.001). Moreover, bed rest increased protein oxidative stress, as measured by muscle protein carbonylation changes (from 0.6 ± 0.1 to 1.00 ± 0.1 Oxydized-to-total protein ratio; P < 0.04).In conclusion, we developed in erythrocytes a new minimally invasive method to determine peptide synthesis rate in human tissues. Application of the new method to skeletal muscle suggests that disuse atrophy is associated to oxidative stress induction as well as to compensatory activation of the glutathione system.

show abstract

“…Whole-body leucine kinetics were measured by simultaneous administration of [1][2][3][4][5][6][7][8][9][10][11][12][13] (19). Two intravenous catheters were placed in opposite arms, one for infusion of labeled compounds and the other for blood sampling.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…Hb Measurements-Glycine was isolated, and derivative enrichment was measured (Metabolic Solutions, Inc) as described previously (19). Heme was extracted from hemolyzed red cells by a previously described method (20).…”

Section: Sample Analysesmentioning

confidence: 99%

Erythropoiesis and Myocardial Energy Requirements Contribute to the Hypermetabolism of Childhood Sickle Cell Anemia

Hibbert¹,

Creary²,

Gee

et al. 2006

J. pediatr. gastroenterol. nutr.

View full text Add to dashboard Cite

Objectives-We hypothesized that an elevated hemoglobin synthesis rate (SynHb) and myocardial oxygen consumption (MVO 2 ) contribute to the excess protein and energy metabolism reported in children with sickle cell anemia.Patients and Methods-Twelve children (6-12 years old) with asymptomatic sickle cell and 9 healthy children matched for age and sex were studied. Measurements were whole-body protein turnover by [1-13 C]leucine, SynHb by [ 15 N]glycine, resting energy expenditure by indirect calorimetry and the systolic blood pressure-heart rate product used as an index of MVO 2 . Protein energy cost was calculated from protein turnover. Statistical analysis included Spearman correlations and partial correlation analyses.Results-Although body mass index was significantly lower for sickle cell versus controls (P < 0.02), children with asymptomatic sickle cell had 52% higher protein turnover (P < 0.0005). Proportional reticulocyte count, SynHb, MVO 2 and resting energy expenditure were also significantly higher in children with sickle cell (P < 0.01). Protein turnover correlated significantly with both SynHb (r = 0.63, P < 0.01) and reticulocyte percentage (r = 0.83, P < 0.0001). Partial correlation of these 3 variables showed reticulocyte percentage as the only variable to be significantly associated with protein turnover, even after adjusting for sickle cell anemia (P = 0.03). Partial correlation of log resting energy expenditure on MVO 2 was significant, controlling for protein energy cost, sex and age (P = 0.03).Conclusion-These results indicate that metabolic demands of increased erythropoiesis and cardiac energy consumption account for much of the excess protein and energy metabolism in children with sickle cell anemia. Homozygous sickle cell disease (HbSS) is characterized by severe chronic hemolytic anemia associated with increased rate of erythropoiesis (1). Resting energy expenditure (REE), whole-body protein turnover (Q) (2-6) and protein catabolism, via increased urea production rate (7,8), are concurrently elevated in patients with HbSS. These findings support the notion that patients with HbSS are hypermetabolic, requiring more dietary protein and energy, compared with healthy controls with normal hemoglobin (Hb) genotype (HbAA). Children with HbSS experience poor growth and development (9), often becoming short thin adults (10). This growth failure may be a direct consequence of inadequate dietary protein and energy. NIH Public AccessBecause protein turnover consumes energy, a direct link between increased REE and elevated erythropoiesis has been inferred; so far, no reports confirm this association (1). Cardiac output is estimated to account for 7% to 33% of REE in healthy adults (11-13), but its contribution to energy requirements of HbSS is not known. Buchowski et al. (14) showed that basal energy requirements were higher than normal for adolescents with HbSS and provided the following simple equation for predicting the REE based on body weight and Hb concentration:The components of this...

show abstract

Measurement of Hemoglobin Synthesis Rate in Vivo Using a Stable Isotope Method

Cited by 3 publications

References 17 publications

Use of an oral stable isotope label to confirm variation in red blood cell mean age that influences HbA1c interpretation

Use of an oral stable isotope label to confirm variation in red blood cell mean age that influences HbA1c interpretation

Effects of inactivity on human muscle glutathione synthesis by a double-tracer and single-biopsy approach

Erythropoiesis and Myocardial Energy Requirements Contribute to the Hypermetabolism of Childhood Sickle Cell Anemia

Contact Info

Product

Resources

About