ArticleThe Journal of clinical investigation2013
Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02146404 (The Effect of Insulin-induced Hypoglycemia on Brain Lactate Accumulation and Regional Cerebral Blood Flow in Patients With Type 1 Diabetes Mellitus With and Without Hypoglycemia Unawareness and Non-diabetic Controls), which is not on this map. Cited by 55 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
The Effect of Insulin-induced Hypoglycemia on Brain Lactate Accumulation and Regional Cerebral Blood Flow in Patients With Type 1 Diabetes Mellitus With and Without Hypoglycemia Unawareness and Non-diabetic Controls
Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- A Systematic Review of Neuroprotective Strategies in the Management of Hypoglycemia.International journal of molecular sciences · 2019Pooled it
- Trial
- Effect of lactate administration on cerebral blood flow during hypoglycemia in people with type 1 diabetes.BMJ open diabetes research & care · 2022Trial
- Influence of Glycemic Control on Endogenous Circulating Ketone Concentrations in Adults Following Traumatic Brain Injury.Neurocritical care · 2017Trial
- Improvement of Neuroenergetics by Hypertonic Lactate Therapy in Patients with Traumatic Brain Injury Is Dependent on Baseline Cerebral Lactate/Pyruvate Ratio.Journal of neurotrauma · 2016Trial
- The role of lactate in retinal health and disease: mechanisms and potential therapeutic strategies. A narrative review.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Review
- Lactate and cognition: a dual modulator.Frontiers in molecular neuroscience · 2026Review
- Hypothalamic Prostaglandins Facilitate Recovery From Severe Hypoglycemia but Exacerbate Recurrent Hypoglycemia in Mice.Diabetes · 2025Article
- Mapping of neurovascular and neurometabolic couplings by multimodal optical imaging.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- Lactate metabolism and histone lactylation in the central nervous system disorders: impacts and molecular mechanisms.Journal of neuroinflammation · 2024Review
- Recent Trends in Nanocarrier-Based Drug Delivery System for Prostate Cancer.AAPS PharmSciTech · 2024Review
- Remembrance of things past: The consequences of recurrent hypoglycaemia in diabetes.Diabetic medicine : a journal of the British Diabetic Association · 2022Review
- Heterogeneity in Epinephrine Response to Experimental Hypoglycemia in Type 1 Diabetes and Controls.Journal of the Endocrine Society · 2022Article
- Clinical evaluation of a novel subcutaneous lactate monitor.Journal of clinical monitoring and computing · 2022Article
- Insulin-Induced Recurrent Hypoglycemia Up-Regulates Glucose Metabolism in the Brain Cortex of Chemically Induced Diabetic Rats.International journal of molecular sciences · 2021Article
- Consequences of recurrent hypoglycaemia on brain function in diabetes.Diabetologia · 2021Review
- Insulin actions on hypothalamic glucose-sensing neurones.Journal of neuroendocrinology · 2021Review
- Dynamic Variations in Brain Glycogen are Involved in Modulating Isoflurane Anesthesia in Mice.Neuroscience bulletin · 2020Article
- Review
- Effect of lactate administration on brain lactate levels during hypoglycemia in patients with type 1 diabetes.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Hypoglycemia occurs frequently during intensive insulin therapy in patients with both type 1 and type 2 diabetes and remains the single most important obstacle in achieving tight glycemic control. Using a rodent model of hypoglycemia, we demonstrated that exposure to antecedent recurrent hypoglycemia leads to adaptations of brain metabolism so that modest increments in circulating lactate allow the brain to function normally under acute hypoglycemic conditions. We characterized 3 major factors underlying this effect. First, we measured enhanced transport of lactate both into as well as out of the brain that resulted in only a small increase of its contribution to total brain oxidative capacity, suggesting that it was not the major fuel. Second, we observed a doubling of the glucose contribution to brain metabolism under hypoglycemic conditions that restored metabolic activity to levels otherwise only observed at euglycemia. Third, we determined that elevated lactate is critical for maintaining glucose metabolism under hypoglycemia, which preserves neuronal function. These unexpected findings suggest that while lactate uptake was enhanced, it is insufficient to support metabolism as an alternate substrate to replace glucose. Lactate is, however, able to modulate metabolic and neuronal activity, serving as a "metabolic regulator" instead.
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What OpenQuestion holds
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.