Sources of hepatic glycogen synthesis following a milk-containing breakfast meal in healthy subjects

Barosa, Cristina; Silva, Claudia; Fagulha, Ana; Barros, Luísa; Caldeira, M.Madalena; Carvalheiro, Manuela; Jones, John G.

doi:10.1016/j.metabol.2011.06.022

Cited by 22 publications

(22 citation statements)

References 13 publications

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“…Thus, the fraction of hepatic glycogen derived from all G6P sources is equivalent to the ratio of position 2 enrichment to body water (Jones et al, 2006b;Soares et al, 2009;Barosa et al, 2012). In humans, exchange of G6P hydrogen 2 and body water is N90% complete (Jones et al, 2006b;Delgado et al, 2009;Barosa et al, 2012). In comparison, the data of this report indicate that this exchange is considerably less extensive in both rat and seabass.…”

Section: G6p-isomerase Transaldolasementioning

confidence: 71%

“…These include the complete exchange of G6P hydrogen 2 and body water via G6P-isomerase so that G6P that is synthesized from unlabeled glucose becomes enriched in position 2 to the same extent as body water while G6P derived via the indirect pathway is also quantitatively enriched in this position. Thus, the fraction of hepatic glycogen derived from all G6P sources is equivalent to the ratio of position 2 enrichment to body water (Jones et al, 2006b;Soares et al, 2009;Barosa et al, 2012). In humans, exchange of G6P hydrogen 2 and body water is N90% complete (Jones et al, 2006b;Delgado et al, 2009;Barosa et al, 2012).…”

Section: G6p-isomerase Transaldolasementioning

confidence: 99%

“…Hydrogens 4, 5 and 6 of G6P can also exchange by a combination of G6P-isomerase and transaldolase activities (Bock et al, 2008;Basu et al, 2009Basu et al, , 2010. In overnight-fasted humans, this exchange accounts for~20% of hepatic G6P following a glucose tolerance test (Delgado et al, 2009) or a mixed meal (Barosa et al, 2012). Transaldolase exchange results in the incorporation of 2 H 2 O or other gluconeogenic tracers into G6P and glycogen without any net indirect pathway flux and therefore results in an overestimation of the indirect pathway contribution by these methods.…”

Section: G6p-isomerase Transaldolasementioning

confidence: 99%

“…Alterations in direct and indirect pathway activities can reflect changes in hepatic insulin actions, such as in insulin-dependent diabetes (Bischof et al, 2002) as well as adaptation to different dietary regimes (Obeid et al, 2005(Obeid et al, , 2006. Deuterated water ( 2 H 2 O) is an inexpensive and versatile tracer for the study of hepatic glycogen synthesis under both natural and artificial feeding conditions (Delgado et al, 2009;Soares et al, 2009Soares et al, , 2012Barosa et al, 2012). Analysis of glycogen positional 2 H-enrichments provides estimates of the fractional synthetic rate as well as direct and indirect pathway contributions to glycogen synthesis (Soares et al, 2009(Soares et al, , 2010.…”

Section: Introductionmentioning

confidence: 99%

“…These assumptions have been tested in humans given an oral glucose tolerance test (OGTT) as well as a regular breakfast meal by monitoring the fate of the deuterium labels of [U-2 H 7 ]glucose following its conversion to UDP-glucose, sampled as urinary glucuronide. Analysis of UDP-glucose 2 H-enrichment revealed that a), exchange of G6P position 2 with body water was essentially complete (Delgado et al, 2009;Barosa et al, 2012) and b),~15-20% of G6P derived from the direct pathway underwent transaldolase exchange activity, resulting in a modest overestimation of indirect pathway and underestimation of direct pathway contributions (Delgado et al, 2009;Barosa et al, 2012). The goal of this study was to apply the same methodology to quantify hepatic glycogenic G6P-fructose-6-phosphate (F6P) and transaldolase exchanges in rats and seabass following a glucose challenge.…”

Section: Introductionmentioning

confidence: 99%

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Disposition of [U-2H7]glucose into hepatic glycogen in rat and in seabass

Martins

Rito

Jarak

et al. 2013

Comparative Biochemistry and Physiology Part A: Molecular &

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The stimulation of hepatic glycogenesis is a ubiquitous response to a glucose challenge and quantifying its contribution to glucose uptake informs its role in restoring euglycemia. Glycogenesis can be quantified with labeled water provided that exchange of glucose-6-phosphate hydrogen 2 (G6P-H2) and body water via glucose-6-phosphate isomerase, and exchange of positions 4, 5 and 6 hydrogens (G6P-H456) via transaldolase, are known. These exchanges were quantified in 24-h fasted rats (Rattus norvegicus; n=6) and 21-day fasted seabass (Dicentrarchus labrax; n=8) by administration of a glucose load (2000mg·kg(-1)) enriched with [U-(2)H7]glucose and by quantifying hepatic glycogen (2)H-enrichments after 2h (rats) and 48h (seabass). Direct pathway contributions of the glucose load to glycogenesis were also estimated. G6P-H2 and body water exchange was 61±1% for rat and 47±3% for seabass. Transaldolase-mediated exchange of G6P-H456 was 5±1% for rat and 10±1% for seabass. Conversion of the glucose load to hepatic glycogen was significant in seabass (249±54mg·kg(-1)) but negligible in rats (12±1mg·kg(-1)). Preload plasma glucose levels were similar for seabass and rats (3.3±0.7 and 4.4±0.1mmol·L(-1), respectively) but post-load plasma glucose was significantly higher in seabass compared to rats (14.6±1.8 versus 5.8±0.3mmol·L(-1), p<0.01). In conclusion, G6P-H2 and body water exchange is incomplete for both species and has to be accounted for in estimating hepatic glycogen synthesis and direct pathway activities with labeled water tracers. Transaldolase-mediated exchange is insignificant. Hepatic direct pathway glycogenesis plays a prominent role in seabass glucose load disposal, but a negligible role in the rat.

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Section: G6p-isomerase Transaldolasementioning

confidence: 71%

Section: G6p-isomerase Transaldolasementioning

confidence: 99%

Section: G6p-isomerase Transaldolasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Disposition of [U-2H7]glucose into hepatic glycogen in rat and in seabass

Martins

Rito

Jarak

et al. 2013

Comparative Biochemistry and Physiology Part A: Molecular &

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Sources of hepatic glycogen synthesis in mice fed with glucose or fructose as the sole dietary carbohydrate

Jarak

Barosa

Martins

et al. 2018

Magnetic Resonance in Med

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Estimating pentose phosphate pathway activity from the analysis of hepatic glycogen ¹³C‐isotopomers derived from [U‐¹³C]fructose and [U‐¹³C]glucose

Belew

Nunzio

Tavares

et al. 2020

Magnetic Resonance in Med

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Purpose The pentose phosphate pathway (PPP) is an important component of hepatic intermediary metabolism. Jin et al developed an elegant 13C‐NMR method for measuring hepatic PPP flux by quantifying the distribution of glucose 13C‐isotopomers formed from [U‐13C]glycerol. We demonstrate that this approach can be extended to exogenous [U‐13C]fructose and [U‐13C]glucose precursors by 13C‐NMR analysis of glycogen. Methods Twelve male C57BL/6 mice fed standard chow were provided a 55/45 mixture of fructose and glucose at 30% w/v in the drinking water for 18 wk. On the evening before sacrifice, the fructose component was enriched with 20% [U‐13C]fructose for 6 mice, while the glucose component was enriched with 20% [U‐13C]glucose for the remaining 6 mice. Mice were allowed to feed and drink naturally overnight, and then, euthanized. Livers were freeze‐clamped and glycogen was extracted and derivatized for 13C NMR spectroscopy. Flux of each sugar into the PPP relative to its incorporation into glycogen was quantified from selected 13C glycogen isotopomer ratios. Results Both [U‐13C]fructose and [U‐13C]glucose precursors yielded glycogen 13C‐isotopomer distributions that were characteristic of PPP activity. The fraction of [U‐13C]glucose utilized by the PPP relative to its conversion to glycogen via the direct pathway was 14 ± 1%, while that from [U‐13C]fructose relative to its conversion to glycogen via the indirect pathway was significantly lower (10 ± 1%, P = .00032). Conclusions Hepatic PPP fluxes from both [U‐13C]glucose and [U‐13C]fructose precursors were assessed by 13C NMR analysis of glycogen 13C‐isotopomers. Glucose‐6‐phosphate generated via glucokinase and the direct pathway is preferentially utilized by the PPP.

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Sources of hepatic glycogen synthesis following a milk-containing breakfast meal in healthy subjects

Cited by 22 publications

References 13 publications

Disposition of [U-2H7]glucose into hepatic glycogen in rat and in seabass

Disposition of [U-2H7]glucose into hepatic glycogen in rat and in seabass

Sources of hepatic glycogen synthesis in mice fed with glucose or fructose as the sole dietary carbohydrate

Estimating pentose phosphate pathway activity from the analysis of hepatic glycogen ¹³C‐isotopomers derived from [U‐¹³C]fructose and [U‐¹³C]glucose

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Sources of hepatic glycogen synthesis following a milk-containing breakfast meal in healthy subjects

Cited by 22 publications

References 13 publications

Disposition of [U-2H7]glucose into hepatic glycogen in rat and in seabass

Disposition of [U-2H7]glucose into hepatic glycogen in rat and in seabass

Sources of hepatic glycogen synthesis in mice fed with glucose or fructose as the sole dietary carbohydrate

Estimating pentose phosphate pathway activity from the analysis of hepatic glycogen 13C‐isotopomers derived from [U‐13C]fructose and [U‐13C]glucose

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Estimating pentose phosphate pathway activity from the analysis of hepatic glycogen ¹³C‐isotopomers derived from [U‐¹³C]fructose and [U‐¹³C]glucose