Unaltered cerebral blood flow during hypoglycemic activation of the sympathochromaffin system in humans
Abstract
To determine if increases in plasma epinephrine and norepinephrine caused by hypoglycemia are associated with increments in cerebral blood flow (CBF), we measured CBF with positron emission tomography in normal humans at ambient fasting arterial plasma glucose levels and at clamped plasma glucose levels of 5.3, 3.5, and 2.8 mmol/l using the hyperinsulinemic, stepped hypoglycemic clamp technique. Despite significant increases in plasma epinephrine to 7,340 +/- 350 (SE) pmol/l and in plasma norepinephrine to 3.32 +/- 0.35 nmol/l, mean hemispheric CBF (41 +/- 1, 49 +/- 1, 48 +/- 2, and 51 +/- 3 ml x 100 g-1 x min-1) remained constant at the ambient (5.2), 5.3, 3.5, and 2.8 mmol/l glycemic levels, respectively. Furthermore, there was no correlation between CBF and either plasma epinephrine levels ranging from 160 to 10,580 pmol/l or plasma norepinephrine levels ranging from 0.56 to 5.10 nmol/l. Failure to demonstrate any dose-response relationship between plasma catecholamine levels and CBF argues against their primary role in cerebrovascular control during hypoglycemia.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
A total of 25 studies (40%) provided data to either calculate or extract the glycaemic threshold for symptom responses to hypoglycaemia.
“A total of 25 studies (40%) provided data to either calculate or extract the glycaemic threshold for symptom responses to hypoglycaemia [6, 13, 16–18, 20, 23, 24, 26, 29, 31, 33–37, 46, 51–53, 56, 57, 58, 63, 68].”
From Glycaemic thresholds for counterregulatory hormone and symptom responses to hypoglycaemia in people with and without type 1 diabetes: a systematic review (2022) · cites this paper as [20]
Previous studies showed that older age and longer diabetes duration were associated with altered counterregulatory hormone and symptom responses.
“previous studies that showed that older age and longer diabetes duration were associated with altered counterregulatory hormone and symptom responses [19–21].”
From Glycaemic thresholds for counterregulatory hormone and symptom responses to hypoglycaemia in people with and without type 1 diabetes: a systematic review (2022) · cites this paper as [20]
Cited by
Sorted by citations
Adaptation in brain glucose uptake following recurrent hypoglycemia.
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.91.20.9352 · Cited by 208 · see citing works
Self-citationActivation of human medial prefrontal cortex during autonomic responses to hypoglycemia
Teves, D., Videen, T. O., Cryer, P. E., & Powers, W. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307048101 · Cited by 138 · see citing works
Self-citationHYPOGLYCEMIA IN CHILDREN WITH TYPE 1 DIABETES MELLITUS
Ryan, C. M., & Becker, D. J. (1999) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(05)70107-9 · Cited by 69 · see citing works
Wolf, T., Lindauer, U., Villringer, A., & Dirnagl, U. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00354-5 · Cited by 63 · see citing works
CNS sensing and regulation of peripheral glucose levels
Levin, B. E., Dunn-Meynell, A. A., & Routh, V. H. (2002) · International review of neurobiology · doi:10.1016/s0074-7742(02)51007-2 · Cited by 54 · see citing works
MacLeod, K. M., Gold, A. E., Ebmeier, K. P., Hepburn, D. A., Deary, I. J., Goodwin, G. M., & Frier, B. M. (1996) · Metabolism · doi:10.1016/s0026-0495(96)90266-8 · Cited by 43 · see citing works
Effects of hypoglycemia on human brain activation measured with fMRI
Anderson, A. W., Heptulla, R. A., Driesen, N. R., Flanagan, D., Goldberg, P. A., Jones, T. W., Rife, F., Sarofin, H., Tamborlane, W. V., Sherwin, R., et al. (2006) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2006.03.013 · Cited by 39 · see citing works
Verhulst, C. E. M., Fabricius, T. W., Teerenstra, S., Kristensen, P. L., Tack, C. J., McCrimmon, R. J., Heller, S., Evans, M. L., Amiel, S. A., Pedersen-Bjergaard, U., et al. (2022) · Diabetologia · doi:10.1007/s00125-022-05749-8 · Cited by 34 · see citing works
Hoffman, R. P. (2006) · Diabetes Care · doi:10.2337/dc06-2460 · Cited by 24 · see citing works
Sustained elevation of cerebral blood flow after hypoglycaemia in normal man
Eckert, B., Ryding, E., & Agardh, C. (1998) · Diabetes Research and Clinical Practice · doi:10.1016/s0168-8227(98)00031-x · Cited by 19 · see citing works
Bie-Olsen, L. G., Kjær, T. W., Pedersen‐Bjergaard, U., Lonsdale, M. N., Holst, J. J., Law, I. G., & Thorsteinsson, B. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22002 · Cited by 18 · see citing works
Kennan, R. P., Jacob, R. J., Sherwin, R. S., et al. (2000) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200009000-00010 · Cited by 16 · see citing works
Cerebral Blood Flow and Metabolism
Powers, W. J. (2015) · Elsevier eBooks · doi:10.1016/b978-0-323-29544-4.00003-7 · Cited by 8 · see citing works
Self-citationCerebral Blood Flow and Metabolism in Human Cerebrovascular Disease
Zazulia, A. R., Markham, J., & Powers, W. J. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4160-5478-8.10004-1 · Cited by 9 · see citing works
Self-citationCerebral Blood Flow and Metabolism in Human Cerebrovascular Disease
Zazulia, A. R., Markham, J., & Powers, W. J. (2004) · Elsevier eBooks · doi:10.1016/b0-44-306600-0/50047-x · Cited by 6 · see citing works
Self-citationAssociation between elevated blood glucose level and brain injuries (IVH/WMI) in preterm infants
Lampe, R., Felderhoff‐Müser, U., Sidorenko, I., Krüger, M., Lück, E., Michales, E., Sassen, U., & Brickmann, C. (2026) · BMC Pediatrics · doi:10.1186/s12887-026-07341-0 · Cited by 1 · see citing works
“By contrast, according to Powers et al. [29] a reduction in arterial glucose concentration below 2.0 mmol/L leads to an increase in CBF.”
Influential
- Authors
- Powers, W. J., Boyle, P. J., Hirsch, I. B., & Cryer, P. E.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 1993-10-01
- Volume
- 265
- Issue
- 4
- Pages
- R883-R887
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2213653541
- Cited by
- 16
- References
- 0
- Citations by year
- 2026: 1 · 2022: 1 · 2015: 1
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ns028700-02)
- National Heart, Lung, and Blood Institute (HL 13851, P01HL013851)
- National Institute of Neurological Disorders and Stroke (NSO6833, NS28700)
- 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 › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- cerebral blood flow, hypoglycemia, epinephrine, norepinephrine, catecholamines, cerebrovascular control, hyperinsulinemic-euglycemic clamp, plasma glucose
- MeSH terms
- Adult, Blood Glucose, Cerebrovascular Circulation, Chromaffin System, Epinephrine, Female, Humans, Hypoglycemia, Male, Norepinephrine, Sympathetic Nervous System
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
