Minireview: The Role of the Autonomic Nervous System in Mediating the Glucagon Response to Hypoglycemia
Open accessAbstract
In type 1 diabetes, the impairment of the glucagon response to hypoglycemia increases both its severity and duration. In nondiabetic individuals, hypoglycemia activates the autonomic nervous system, which in turn mediates the majority of the glucagon response to moderate and marked hypoglycemia. The first goal of this minireview is therefore to illustrate and document these autonomic mechanisms. Specifically we describe the hypoglycemic thresholds for activating the three autonomic inputs to the islet (parasympathetic nerves, sympathetic nerves, and adrenal medullary epinephrine) and their magnitudes of activation as glucose falls from euglycemia to near fatal levels. The implication is that their relative contributions to this glucagon response depend on the severity of hypoglycemia. The second goal of this minireview is to discuss known and suspected down-regulation or damage to these mechanisms in diabetes. We address defects in the central nervous system, the peripheral nervous system, and in the islet itself. They are categorized as either functional defects caused by glucose dysregulation or structural defects caused by the autoimmune attack of the islet. In the last section of the minireview, we outline approaches for reversing these defects. Such reversal has both scientific and clinical benefit. Scientifically, one could determine the contribution of these defects to the impairment of glucagon response seen early in type 1 diabetes. Clinically, restoring this glucagon response would allow more aggressive treatment of the chronic hyperglycemia that is linked to the debilitating long-term complications of this disease.
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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 [24]
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- Authors
- Taborsky, G. J., & Mundinger, T. O.
- Affiliations
- University of Washington (US)
- Corresponding author
- Taborsky, Gerald J.
- ORCID
- Mundinger, Thomas O.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2012-03-01
- Volume
- 153
- Issue
- 3
- Pages
- 1055-1062
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC3384078
- OpenAlex
- W2013974905
- Cited by
- 140
- References
- 34
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 7 · 2023: 14 · 2022: 8 · 2021: 9 · 2020: 6 · 2019: 7 · 2018: 11 · 2017: 3 · 2016: 9 · 2015: 11 · 2014: 16 · 2013: 17 · 2012: 5
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK050154, P30DK017047)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- glucagon response, hypoglycemia, autonomic nervous system, type 1 diabetes, parasympathetic nerves, sympathetic nerves, adrenal medulla, epinephrine, pancreatic islets, autonomic dysfunction, islet autoimmunity, hyperglycemia, late complications
- MeSH terms
- Animals, Autonomic Nervous System, Central Nervous System, Diabetes Mellitus, Diabetes Mellitus, Type 1, Gene Expression Regulation, Glucagon, Glucose, Humans, Hypoglycemia, Insulin Resistance, Islets of Langerhans, Models, Biological, Autoimmunity, Peripheral Nervous System
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