Pyruvate Administered After Severe Hypoglycemia Reduces Neuronal Death and Cognitive Impairment
Open accessAbstract
Hypoglycemia-induced brain injury is a significant obstacle to optimal blood glucose control in diabetic patients. Severe hypoglycemia triggers a cascade of events in vulnerable neurons that may culminate in cell death even after glucose normalization. A key event in this cascade is the activation of poly(ADP-ribose) polymerase-1 (PARP-1). Activated PARP-1 consumes cytosolic NAD, and because NAD is required for glycolysis, hypoglycemia-induced PARP-1 activation may render cells unable to use glucose even when glucose availability is restored. Pyruvate, however, can be metabolized in the absence of cytosolic NAD. Here we tested whether pyruvate could improve the outcome in rats subjected to insulin-induced hypoglycemia by terminating hypoglycemia with either glucose alone or glucose plus pyruvate. In the four brain regions studied—CA1, subiculum, dentate gyrus of the hippocampus, and piriform cortex—the addition of pyruvate reduced neuron death by 70–90%. Improved neuron survival was also observed when pyruvate delivery was delayed for up to 3 h. The improved neuron survival was accompanied by a sustained improvement in cognitive function as assessed by the Morris water maze. These results suggest that pyruvate may significantly improve the outcome after severe hypoglycemia by circumventing a sustained impairment in neuronal glucose utilization resulting from PARP-1 activation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Administration of pyruvate significantly improved neuronal survival in the brains of rats subjected to insulin-induced hypoglycemia.
“administration of pyruvate significantly improved neuronal survival in the brains of rats subjected to insulin-induced hypoglycemia (Suh et al., 2005).”
From Human ApoE Isoforms Differentially Modulate Brain Glucose and Ketone Body Metabolism: Implications for Alzheimer's Disease Risk Reduction and Early Intervention (2018) · cites this paper as Suh et al., 2005
The title in our copy states that pyruvate administered after severe hypoglycemia reduces neuronal death, supporting the neuronal-survival point. The available passages do not establish that the subjects were rats, that hypoglycemia was insulin-induced, or that the improvement was statistically significant. (LLM, conf=0.82)
Experimental — accuracy not yet measuredOveractivation of poly (ADP-ribose) polymerase-1 (PARP-1) resulted in the depletion of cytosolic NAD+ followed by inhibition of glycolysis, leading to sustained energy failure and ultimately cell death.
“Suh et al. (2005) reported that the overactivation of poly (ADP-ribose) polymerase-1 (PARP-1) resulted in the depletion of cytosolic NAD ϩ followed by inhibition of glycolysis, leading to sustained energy failure and ultimately cell death.”
From Human ApoE Isoforms Differentially Modulate Brain Glucose and Ketone Body Metabolism: Implications for Alzheimer's Disease Risk Reduction and Early Intervention (2018) · cites this paper as Suh et al. (2005)
The available copy contains bibliographic information for Suh et al. (2005), but no passage addressing the proposed mechanism. Searches for PARP-1, cytosolic NAD+ depletion, glycolysis inhibition, and sustained energy failure found no relevant passage, so the attribution cannot be verified from this copy. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Pellerin, L., & Magistretti, P. J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.22.10625 · Cited by 2,927 · see citing works
Mediation of Poly(ADP-Ribose) Polymerase-1-Dependent Cell Death by Apoptosis-Inducing Factor
Yu, S.-W., Wang, H., Poitras, M. F., Coombs, C., Bowers, W. J., Federoff, H. J., Poirier, G. G., Dawson, T. M., & Dawson, V. L. (2002) · Science · doi:10.1126/science.1072221 · Cited by 1,826 · see citing works
Carrier-mediated blood-brain barrier transport of short-chain monocarboxylic organic acids
Oldendorf, W. (1973) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1973.224.6.1450 · Cited by 463 · cited 2× · see citing works
“Because pyruvate crosses the blood-brain barrier by both facilitated transport and diffusion (25,26), this increase in plasma concentration should substantially increase pyruvate transport into brain.”
Flagged first, then by citations
Cited by
Sorted by citations
Ying, W. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1672 · Cited by 1,494 · see citing works
Myelination and the trophic support of long axons
Nave, K.-A. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2797 · Cited by 648 · see citing works
Suh, S. W., Gum, E. T., Hamby, A. M., Chan, P. H., & Swanson, R. A. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30077 · Cited by 419 · see citing works
Self-citationWu, L., Zhang, X., & Zhao, L. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.2262-17.2018 · Cited by 185 · see citing works
Mini-review: Impact of recurrent hypoglycemia on cognitive and brain function
McNay, E. C., & Cotero, V. E. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2010.01.004 · Cited by 111 · see citing works
Puente, E. C., Silverstein, J., Bree, A. J., Musikantow, D. R., Wozniak, D. F., Maloney, S., Daphna-Iken, D., & Fisher, S. J. (2010) · Diabetes · doi:10.2337/db09-1495 · Cited by 103 · see citing works
Deuterium metabolic imaging reports on tert expression and early response to therapy in cancer
Batsios, G., Taglang, C., Tran, M., Stevers, N., Barger, C., Gillespie, A. M., Ronen, S. M., Costello, J. F., & Viswanath, P. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-4418 · Cited by 40 · see citing works
- Authors
- Suh, S. W., Aoyama, K., Matsumori, Y., Liu, J., & Swanson, R. A.
- Affiliations
- San Francisco VA Medical Center (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2005-05-01
- Volume
- 54
- Issue
- 5
- Pages
- 1452-1458
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2122914502
- Cited by
- 135
- References
- 3
- Citations by year
- 2026: 8 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 3 · 2019: 5 · 2018: 9 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 5 · 2013: 9 · 2012: 3
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- green
- pure.teikyo.jp
- Licence
- cc-by-nc-nd
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Funders
- U.S. Department of Veterans Affairs
- National Institute of Neurological Disorders and Stroke (R01NS041421)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Neurological and metabolic disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Keywords
- pyruvate, hypoglycemia, hypoglycemic brain injury, PARP1, NAD+ depletion, neuronal cell death, cognitive impairment, insulin-induced hypoglycemia, hippocampus, piriform cortex, glucose metabolism, neuroprotection
- MeSH terms
- Animals, Cognition Disorders, Disease Models, Animal, Hypoglycemia, Insulin, Ketoglutaric Acids, Neurons, Cell Death, Pyruvic Acid, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
