Glycerol's contribution to lactate production outside of a glucose intermediate in fasting humans

Shah, Ankit; Wang, Yujue; Su, Xiaoyang; Wondisford, Fredric E.

doi:10.1016/j.metabol.2022.155214

Cited by 7 publications

(2 citation statements)

References 36 publications

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“…Glycerol presents a viscous liquid with very broad applications in cosmetics, medicine, and lubricants. − Therefore, glycerol and water systems were selected as viscosity-measured media due to their simple operation, good stability, tunable value, and high accuracy. At first, we prepared the solution of glycerol/H 2 O with various volume ratios, and accurately measured their viscosity values through a viscometer at room temperature, respectively.…”

Section: Resultsmentioning

confidence: 99%

Viscosity-Responsive Electrochemiluminescence of Diphenylbenzofulvene Derivatives

Han

Chai

et al. 2023

Anal. Chem.

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The development of superior probes is highly desirable and valuable for viscosity measurement. Herein, we designed and reported a series of diphenylbenzofulvene (DPBF)-based organic luminophores according to the molecular regulation strategy. There are two free-rotating phenyl groups attached to the rigid fluorene skeleton in the DPBF, enabling its unique propeller-like noncoplanar chemical structure. Benefiting from this, DPBFs could feature outstanding PL and ECL emissions with intriguing aggregation-induced characteristics. Experimental and theoretical investigations revealed that substituent, spatial structure, and molecular orbital energy profoundly affected their luminescent behaviors. It was disclosed that fluoro-substituted DPBF(F)2 with a smaller LUMO–HOMO band gap demonstrated the strongest ECL emission and was selected as the optimal ECL emitter. Finally, DPBF(F)2 featured a linear response to the viscosity and VC content with lower limits of detection (LOD) of 5.69 μcP and 38.2 nM, respectively. This study represents the first example of the ECL probe toward viscosity and will be of great significance for both ECL application and viscosity measurement.

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Section: Resultsmentioning

confidence: 99%

Viscosity-Responsive Electrochemiluminescence of Diphenylbenzofulvene Derivatives

Han

Chai

et al. 2023

Anal. Chem.

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“…Glycerol is a well-known contributor to gluconeogenesis in the liver. We also recently showed in mice [ 1 ] and humans [ 2 ] that glycerol can bypass glucose and convert directly to lactate, a glycolytic intermediate.…”

Section: Introductionmentioning

confidence: 99%

Differential Metabolism of Glycerol Based on Oral versus Intravenous Administration in Humans

2022

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Glycerol can be metabolized to glucose via gluconeogenesis or lactate via glycolysis. It is unknown if glycerol is metabolized similarly in the portal and systemic circulations in humans. Eight metabolically healthy overnight-fasted individuals received equimolar amounts of 13C3-glycerol orally and intravenously on two separate occasions with serial blood draws over four hours. Serum samples underwent liquid chromatography–mass spectrometry analysis. Oral 13C3-glycerol administration led to higher average serum glucose enrichment than intravenous administration (5.02 ± 1.43 versus 4.07 ± 0.79%, p = 0.009). In contrast, intravenous 13C3-glycerol administration yielded higher average serum lactate enrichment than oral administration (5.67 ± 0.80 versus 4.85 ± 1.30%, p = 0.032). Peak serum glucose enrichment was also higher with oral administration (9.37 ± 2.93 versus 7.12 ± 1.28%, p = 0.010). Glycerol metabolism across the portal and systemic circulations is not congruent. Orally administered labeled glycerol led to greater labeled glucose production, while intravenously administration yielded greater lactate production. These data support direct glycerol to lactate conversion in humans.

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In vivo glycerol metabolism in patients with glycerol kinase deficiency

Shah,

Xu,

Kwon

et al. 2024

JIMD Reports

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Glycerol kinase deficiency (GKD) is an X‐linked recessive disorder due to glycerol kinase (GK) gene mutations resulting in hyperglycerolermia, hyperglyceroluria, and “pseudohypertriglyceridemia.” In vivo glycerol metabolism has not been assessed in GKD. A 62‐year‐old man with suspected GKD and his extended family underwent whole exome sequencing and fasting blood work with two modes of lipid measurements: (1) standard lipase‐based methodology and (2) nuclear magnetic resonance (NMR). Two overnight fasted men with GKD and a heterozygote female carrier then underwent 13C3‐glycerol infusion. Affected family members had a novel two‐nucleotide deletion in exon 5 of the GK gene (c.373_374del). Compared to their family members (n = 14), men with GKD (n = 5) had significantly lower total cholesterol levels (3.72 ± 0.70 vs. 4.77 ± 0.85 mmol/L, p = 0.024). Compared to NMR, lipase‐based assays overreported triglycerides (5.28 ± 1.38 vs. 0.81 ± 0.32, mmol/L, p < 0.001) and underreported low‐density lipoprotein cholesterol values (0.93 ± 0.23 vs. 2.18 ± 0.42 mmol/L, p = 0.001) in GKD. Men with GKD could not convert glycerol into glucose or triglycerides, which was preserved in the heterozygote carrier. Glycolytic metabolism of glycerol to lactate persisted in GKD, but it was reduced by a magnitude and, possibly, due to homologous glycerol kinases encoded by other genes. In summary, we report a novel GK pathogenic variant; affected men cannot convert circulating glycerol to glucose or triglycerides and have lower cholesterol levels. These results offer a human model for potentially targeting glycerol kinase to treat conditions associated with hyperglycemia and hyperlipidemia and warrant further investigation.

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Glycerol's contribution to lactate production outside of a glucose intermediate in fasting humans

Cited by 7 publications

References 36 publications

Viscosity-Responsive Electrochemiluminescence of Diphenylbenzofulvene Derivatives

Viscosity-Responsive Electrochemiluminescence of Diphenylbenzofulvene Derivatives

Differential Metabolism of Glycerol Based on Oral versus Intravenous Administration in Humans

In vivo glycerol metabolism in patients with glycerol kinase deficiency

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