ArticleThe Journal of clinical investigation2019
Regulation of hepatic mitochondrial oxidation by glucose-alanine cycling during starvation in humans.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 67 citations in OpenAlex.
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- Association of three different dietary patterns with the metabolomic profiles of children: the BiomarKid project.European journal of nutrition · 2026Article
- Metformin's disruption of gluconeogenesis in type 2 diabetes impairments of the cori and alanine cycles as hidden drivers of metabolic waste accumulation, NF-κBHIF-1α-mediated low-grade inflammation, and multisystem dysfunction.Problemy endokrinologii · 2026Review
- Lactate metabolism reprogramming through orthogonal tandem catalysis to reverse intervertebral disc degeneration.Nature communications · 2026Article
- Repeated administration of L-alanine to mice reduces behavioural despair and increases hippocampal mammalian target of rapamycin signalling: Analysis of gender and metabolic effects.Journal of psychopharmacology (Oxford, England) · 2025Article
- Cancer cachexia: multilevel metabolic dysfunction.Nature metabolism · 2024Review
- Type 1 Diabetes and Cataracts: Investigating Mediating Effects of Serum Metabolites Using Bidirectional Mendelian Randomization.Metabolites · 2024Article
- Knockout of the Muscle-Specific E3 Ligase MuRF1 Affects Liver Lipid Metabolism upon Dexamethasone Treatment in Mice.ACS omega · 2024Article
- Sepsis-induced changes in pyruvate metabolism: insights and potential therapeutic approaches.EMBO molecular medicine · 2024Review
- GC/MS-Based Metabolomic Analysis of A549 Cells Exposed to Emerging Organophosphate Flame Retardants.Toxics · 2024Article
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- Hepatic malonyl-CoA synthesis restrains gluconeogenesis by suppressing fat oxidation, pyruvate carboxylation, and amino acid availability.Cell metabolism · 2024Article
- Metabolic predictors of COVID-19 mortality and severity: a survival analysis.Frontiers in immunology · 2024Article
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- Liver mitochondrial cristae organizing protein MIC19 promotes energy expenditure and pedestrian locomotion by altering nucleotide metabolism.Cell metabolism · 2023Article
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- Persistent fasting lipogenesis links impaired ketogenesis with citrate synthesis in humans with nonalcoholic fatty liver.The Journal of clinical investigation · 2023Observational
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4 authors at 2 institutions in 1 country.
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Abstract
In order to determine whether the glucose-alanine cycle regulates rates of hepatic mitochondrial oxidation in humans, we applied positional isotopomer NMR tracer analysis (PINTA) to assess rates of hepatic mitochondrial oxidation and pyruvate carboxylase flux in healthy volunteers following both an overnight (12 hours) and a 60-hour fast. Following the 60-hour fast, rates of endogenous glucose production and mitochondrial oxidation decreased, whereas rates of hepatic pyruvate carboxylase flux remained unchanged. These reductions were associated with reduced rates of alanine turnover, assessed by [3-13C]alanine, in a subgroup of participants under similar fasting conditions. In order to determine whether this reduction in alanine turnover was responsible for the reduced rates of hepatic mitochondrial oxidation, we infused unlabeled alanine into another subgroup of 60-hour fasted subjects to increase rates of alanine turnover, similar to what was measured after a 12-hour fast, and found that this perturbation increased rates of hepatic mitochondrial oxidation. Taken together, these studies demonstrate that 60 hours of starvation induce marked reductions in rates of hepatic mitochondrial oxidation, which in turn can be attributed to reduced rates of glucose-alanine cycling, and reveal a heretofore undescribed role for glucose-alanine in the regulation of hepatic mitochondrial oxidation in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.