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Cited by 208Diabetes Management and ResearchNeurological and metabolic disordersPancreatic function and diabetes

Adaptation in brain glucose uptake following recurrent hypoglycemia.

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Boyle, P J, Nagy, R J, O'Connor, A M, Kempers, S F, Yeo, R A, Qualls, C·1994·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.91.20.9352PMC PMC44810
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Abstract

Brain glucose metabolism is impaired during hypoglycemia, but, if sustained, brain metabolism reverts to normal in animal models--data in man are lacking. We tested the hypothesis that adaptations occur to allow maintenance of normal rates of brain glucose uptake (BGU) following recurrent hypoglycemia in man. Twelve normal humans were studied over 4 days. On the initial day, arterial plasma glucose concentrations were decreased from 4.72 to 2.50 mmol/liter in five 0.56 mmol/liter steps. Cerebral blood flow, brain arteriovenous glucose difference, BGU, and cognitive function were quantitated at each step. BGU was initially impaired at the 3.61 mmol/liter glucose step (P = 0.04) and was antedated by increments in epinephrine that began at 4.16 mmol/liter (P = 0.03). The onset of hypoglycemic symptoms occurred during the 3.61 mmol/liter glucose step (P = 0.02), whereas tests of cognitive function generally deteriorated at the 3.05 mmol/liter step (P < 0.05). During the next 56 hr, mean glucose concentrations were kept at 2.9 +/- 0.1 mmol/liter and reached normal only during meals. The stepped clamp protocol was repeated beginning at 4.16 mmol/liter on the last day. No decrement in BGU was observed at any step; cognitive function was preserved until significantly lower glucose concentrations on the final day relative to the first (P = 0.04). Subjects remained asymptomatic of hypoglycemia until they reached a glucose concentration of 2.50 mmol/liter (P < 0.001 vs. day 1), while initial increments in all counterregulatory hormones were forestalled to lower glucose steps than on day 1. Therefore, adaptations occur that allow normal BGU and cerebral function to be maintained during recurrent systemic hypoglycemia. Counterregulatory events that should result in symptoms of hypoglycemia and increments in endogenous glucose production are prevented until extremely subnormal glucose concentrations.

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Authors
Boyle, P. J., Nagy, R. J., O'Connor, A. M., Kempers, S. F., Yeo, R. A., & Qualls, C.
Affiliations
University of New Mexico (US)
ORCID
Qualls, C
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1994-09-27
Volume
91
Issue
20
Pages
9352-9356
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.91.20.9352
PMC
PMC44810
OpenAlex
W2093219766
Cited by
208
References
45
Citations by year
2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 4 · 2019: 4 · 2018: 7 · 2017: 9 · 2016: 8 · 2015: 6 · 2014: 4 · 2013: 12 · 2012: 13
FWCI
4.98
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r29ns029972-05)
  • National Institute of Neurological Disorders and Stroke (1 R29 NS29972-01A1)
  • National Center for Research Resources (5 M01 RR00997-17, M01RR000997)
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 › Surgery › Pancreatic function and diabetes
Keywords
recurrent hypoglycemia, brain glucose uptake, brain glucose metabolism, epinephrine, cognitive function, cerebral blood flow, arteriovenous glucose difference, hypoglycemic symptoms, endogenous glucose production
MeSH terms
Acclimatization, Adult, Blood Glucose, Brain, Cognition, Epinephrine, Female, Glucagon, Glucose, Humans, Hydrocortisone, Hypoglycemia, Insulin, Male, Memory, Norepinephrine, Pancreatic Polypeptide, Reference Values, Regional Blood Flow, Growth Hormone, Glucose Clamp Technique

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