ArticleThe Biochemical journal2012
Effects of a glucokinase activator on hepatic intermediary metabolism: study with 13C-isotopomer-based metabolomics.
Article in The Biochemical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Efficacy and safety of dorzagliatin for type 2 diabetes mellitus: A meta-analysis and trial sequential analysis.Frontiers in cardiovascular medicine · 2022Pooled it
- Transgenerational memory deficits in cocaine-sired male rat offspring and grand-offspring.Addiction neuroscience · 2026Article
- G6PC2 controls glucagon secretion by defining the set point for glucose in pancreatic α cells.Science translational medicine · 2025Article
- Current Insight on the Role of Glucokinase and Glucokinase Regulatory Protein in Diabetes.Mini reviews in medicinal chemistry · 2024Review
- From Non-Alcoholic Fatty Liver to Hepatocellular Carcinoma: A Story of (Mal)Adapted Mitochondria.Biology · 2023Review
- Transcriptome and metabolome after porcine hemodynamic-directed CPR compared with standard CPR and sham controls.Resuscitation plus · 2022Article
- Disruptions in hepatic glucose metabolism are involved in the diminished efficacy after chronic treatment with glucokinase activator.PloS one · 2022Article
- Maintaining Effective Beta Cell Function in the Face of Metabolic Syndrome-Associated Glucolipotoxicity-Nutraceutical Options.Healthcare (Basel, Switzerland) · 2021Review
- Dimethyl Fumarate, an Approved Multiple Sclerosis Treatment, Reduces Brain Oxidative Stress in SIV-Infected Rhesus Macaques: Potential Therapeutic Repurposing for HIV Neuroprotection.Antioxidants (Basel, Switzerland) · 2021Article
- Malic Enzyme Couples Mitochondria with Aerobic Glycolysis in Osteoblasts.Cell reports · 2020Article
- Collapse of the hepatic gene regulatory network in the absence of FoxA factors.Genes & development · 2020Article
- Targeting glutamine metabolism slows soft tissue sarcoma growth.Nature communications · 2020Article
- Fructose-1,6-Bisphosphatase 2 Inhibits Sarcoma Progression by Restraining Mitochondrial Biogenesis.Cell metabolism · 2020Article
- A constitutive knockout of murine carbamoyl phosphate synthetase 1 results in death with marked hyperglutaminemia and hyperammonemia.Journal of inherited metabolic disease · 2019Article
- HCF-1 Regulates De Novo Lipogenesis through a Nutrient-Sensitive Complex with ChREBP.Molecular cell · 2019Article
- Ex vivo and in vivo stable isotope labelling of central carbon metabolism and related pathways with analysis by LC-MS/MS.Nature protocols · 2019Article
- Control of glucose metabolism is important in tenogenic differentiation of progenitors derived from human injured tendons.PloS one · 2019Article
- The Central Role of Glucokinase in Glucose Homeostasis: A Perspective 50 Years After Demonstrating the Presence of the Enzyme in Islets of Langerhans.Frontiers in physiology · 2019Review
- L-leucine stimulates glutamate dehydrogenase activity and glutamate synthesis by regulating mTORC1/SIRT4 pathway in pig liver.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2018Article
- Conditional disruption of hepatic carbamoyl phosphate synthetase 1 in mice results in hyperammonemia without orotic aciduria and can be corrected by liver-directed gene therapy.Molecular genetics and metabolism · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
GKAs (glucokinase activators) are promising agents for the therapy of Type 2 diabetes, but little is known about their effects on hepatic intermediary metabolism. We monitored the fate of (13)C-labelled glucose in both a liver perfusion system and isolated hepatocytes. MS and NMR spectroscopy were deployed to measure isotopic enrichment. The results demonstrate that the stimulation of glycolysis by GKA led to numerous changes in hepatic metabolism: (i) augmented flux through the TCA (tricarboxylic acid) cycle, as evidenced by greater incorporation of (13)C into the cycle (anaplerosis) and increased generation of (13)C isotopomers of citrate, glutamate and aspartate (cataplerosis); (ii) lowering of hepatic [Pi] and elevated [ATP], denoting greater phosphorylation potential and energy state; (iii) stimulation of glycogen synthesis from glucose, but inhibition of glycogen synthesis from 3-carbon precursors; (iv) increased synthesis of N-acetylglutamate and consequently augmented ureagenesis; (v) increased synthesis of glutamine, alanine, serine and glycine; and (vi) increased production and outflow of lactate. The present study provides a deeper insight into the hepatic actions of GKAs and uncovers the potential benefits and risks of GKA for treatment of diabetes. GKA improved hepatic bioenergetics, ureagenesis and glycogenesis, but decreased gluconeogenesis with a potential risk of lactic acidosis and fatty liver.
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Registered trials
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