The physiology and pathophysiology of the neural control of the counterregulatory response
Abstract
Despite significant technological and pharmacological advancements, insulin replacement therapy fails to adequately replicate β-cell function, and so glucose control in type 1 diabetes mellitus (T1D) is frequently erratic, leading to periods of hypoglycemia. Moreover, the counterregulatory response (CRR) to falling blood glucose is impaired in diabetes, leading to an increased risk of severe hypoglycemia. It is now clear that the brain plays a significant role in the development of defective glucose counterregulation and impaired hypoglycemia awareness in diabetes. In this review, the basic intracellular glucose-sensing mechanisms are discussed, as well as the neural networks that respond to and coordinate the body's response to a hypoglycemic challenge. Subsequently, we discuss how the body responds to repeated hypoglycemia and how these adaptations may explain, at least in part, the development of impaired glucose counterregulation in diabetes.
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The central nervous system modulates glucagon secretion, increasing the complexity and difficulties of identifying a transport model.
“In addition, the central nervous system also modulates glucagon secretion,24,25 which increases the complexity and difficulties of identifying a transport model.”
From Pharmacokinetics Modeling of Exogenous Glucagon in Type 1 Diabetes Mellitus Patients (2013) · cites this paper as [25]
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- Authors
- Beall, C., Ashford, M. L., & McCrimmon, R. J.
- Affiliations
- University of Dundee (GB)
- Corresponding author
- McCrimmon, Rory J.
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2012-01-15
- Volume
- 302
- Issue
- 2
- Pages
- R215-R223
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2103461975
- Semantic Scholar
- 17e7fcd7dfc7fa0e2d03d94c1bfab6b1059f120f
- Cited by
- 63
- References
- 122
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 8 · 2016: 7 · 2015: 4 · 2014: 2 · 2013: 11
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- counterregulatory response, type 1 diabetes, hypoglycemia, hypoglycemia awareness, glucose detection, artificial neural networks, insulin replacement therapy, beta-cell function
- MeSH terms
- Adaptation, Physiological, Blood Glucose, Brain, Diabetes Mellitus, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin
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