Cited by 164Diabetes Management and ResearchPancreatic function and diabetesNeuroscience of respiration and sleep

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Neuroendocrine responses to hypoglycemia

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Tesfaye, Nolawit, Seaquist, Elizabeth R.·2010·Annals of the New York Academy of Sciences

DOI 10.1111/j.1749-6632.2010.05820.xPMC PMC2991551

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Abstract

The counterregulatory response to hypoglycemia is a complex and well-coordinated process. As blood glucose concentration declines, peripheral and central glucose sensors relay this information to central integrative centers to coordinate neuroendocrine, autonomic, and behavioral responses and avert the progression of hypoglycemia. Diabetes, both type 1 and type 2, can perturb these counterregulatory responses. Moreover, defective counterregulation in the setting of diabetes can progress to hypoglycemia unawareness. While the mechanisms that underlie the development of hypoglycemia unawareness are not completely known, possible causes include altered sensing of hypoglycemia by the brain and/or impaired coordination of responses to hypoglycemia. Further study is needed to better understand the intricacies of the counterregulatory response and the mechanisms contributing to the development of hypoglycemia unawareness.

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“A decrease in blood glucose below the physiological range results in a sequence of counterregulatory responses, initiated by activation of glucose sensors throughout the body (2, 3).”
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Whole genome expression profiling associates activation of unfolded protein response with impaired production and release of epinephrine after recurrent hypoglycemia
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“Increasing evidence indicates their dominant role in the detection of hypoglycemia and initiation of CRR ([12], [13], [14], [15], [5], [16], [17], [18], [19], [20]).”
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“In individuals living with T1D, recurrent hypoglycemia has been shown to reduce the glucose level that precipitates the counter-regulatory response necessary to restore euglycemia during a subsequent episode of hypoglycemia [5–9].”
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“…hepatic glucose production, the activation of the hypothalamus – pituitary – adrenal (HPA) axis to stimulate epinephrine and glucocorticoid secretion (Tesfaye & Seaquist, 2010), and the activation of hypothalamic vasopressin (AVP) neurons to stimulate GCG secretion through the actions of AVP on…”
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“Hypoglycemia activates many counterregulatory mechanisms like decrease in insulin, increase in glucagon and epinephrine secretion, and modulation of the autonomic nervous system (Fanelli et al., 1994; Jensen et al., 2014; Mitrakou et al., 1991; Schwartz et al., 1987; Tesfaye and Seaquist, 2010).”
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“Although cortisol and growth hormone do not have a role in the acute metabolic counterregulatory response to insulin-induced hypoglycemia, they stimulate glucose production and limit glucose uptake over a longer period of time (16, 44).”
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“38,39 42 Therefore, ECM-recapitulating system is essential for accurately modeling brain metabolic disorders in vitro.”
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“8 mmol/L), a highly coordinated neural counterregulatory reflex is triggered which activates the sympathoadrenal system [4].”
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“8 mmol/l (68 mg/dl), and the three efferent components of the autonomic nervous system, the adrenomedullary, sympathetic neural, and parasympathetic neural responses become activated [9,10].”
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“Signs and symptoms of hypoglycemia are categorized as neurogenic or neuroglycopenic (TABLE 2).(1,29,31) Neurogenic symptoms, which largely manifest as increased sympathetic neural activity, trigger increased serum epinephrine levels and exhibit symptoms such as palpitations, anxiety, tremors, tachycardia, and behavior…”
Background
Growth hormone receptor (GHR)-expressing neurons in the hypothalamic arcuate nucleus regulate glucose metabolism and energy homeostasisPreprint
de Lima, J. B. M., Debarba, L. K., Khan, M. M., Ubah, C., Didyuk, O., AYYAR, I. T., Koch, M., & Sadagurski, M. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.17.254862 · Cited by 3
“This effect is complementary to the counter318 regulatory enhancing effect of GH axis during hypoglycemia (42).”
Background
Adult oligodendrogenesis gates arcuate neuronal glucose sensing through remodelling of the blood-hypothalamus barrier via ADAMTS4Preprint
Buller, S. A., Staricoff, E. O., Riches, C. H., Tsang, A. H. K., Josipović, M., Ikemura, K., Opoku, G., Sato, I., Hirohata, S., Stenzel, S., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.10.612227 · Cited by 3
“The brain plays a cri9cal role in the regula9on of glucose homeostasis, not only by regula9ng pancrea9c insulin release and peripheral insulin ac9on 1 , but also through its key role in moun9ng the neuroendocrine counterregulatory response to hypoglycaemia 2 .”
BackgroundMethod
Complicaciones metabólicas agudas. Hiperglucemias e hipoglucemias. Actitudes diagnósticas, tratamiento y situaciones especiales
Cantero, A. P., Sampalo, A. L., Quirantes, P. L., & Jansen‐Chaparro, S. (2020) · Medicine - Programa de Formación Médica Continuada Acreditado · doi:10.1016/j.med.2020.09.022 · Cited by 3
Reversible central adrenal insufficiency induced by recurrent insulinoma-related hypoglycemia: a case report and physiological modeling
Missaoui, A. M., Belabed, W., & Mnif, F. (2025) · The Egyptian Journal of Internal Medicine · doi:10.1186/s43162-025-00458-1 · Cited by 2
“…response to hypoglycemia is a highly complex and well-coordinated physiological process, which involves the inhibition of endogenous insulin secretion and induction of counterregulatory hormone cascade: glucagon, epinephrine, norepinephrine, growth hormone (GH), and cortisol [17].”
The role of the central nervous system in glucose homeostasis
Muntean, C., Moța, M., Popa, S. G., & Mitrea, A. (2012) · Romanian Journal of Diabetes Nutrition and Metabolic Diseases · doi:10.2478/v10255-012-0025-1 · Cited by 2
“Finally the adrenal glands response to hyperglycemia mediated by splanchnic nerves and lumbar ganglia consists of increased epinephrine and glucocorticoids secretion [1, 7, 22, 23].”
Background
Metabolism
Saghiv, M. S., & Sagiv, M. S. (2020) · Springer eBooks · doi:10.1007/978-3-030-48806-2_2 · Cited by 2
Atypical hypoadrenocorticism presenting with hypoglycaemic seizures and bilateral cortical blindness in a dog
Harper, J., & Burchell, R. K. (2023) · Veterinary Record Case Reports · doi:10.1002/vrc2.565 · Cited by 2

Authors: Tesfaye, N., & Seaquist, E. R.
Affiliations: University of Minnesota (US)
Corresponding author: Seaquist, Elizabeth R.
ORCID: Seaquist, Elizabeth R.
Venue: Annals of the New York Academy of Sciences
Publisher: Wiley
Published: 2010-10-29
Volume: 1212
Issue: 1
Pages: 12-28
ISSN: 0077-8923 (ISSN-L)
1749-6632
DOI: 10.1111/j.1749-6632.2010.05820.x
PMC: PMC2991551
OpenAlex: W1800997121
Cited by: 164
References: 140
Citations by year: 2026: 7 · 2025: 15 · 2024: 8 · 2023: 13 · 2022: 10 · 2021: 24 · 2020: 26 · 2019: 10 · 2018: 7 · 2017: 12 · 2016: 4 · 2015: 6 · 2014: 4 · 2013: 7 · 2012: 4
FWCI: 0.82
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Annals of the New York Academy of Sciences (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (2 T32 DK7203-33, T32DK007203)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
Keywords: hypoglycemia, counterregulatory response, neuroendocrine response, autonomic responses, glucose detection, hypoglycemia unawareness, type 1 diabetes, type 2 diabetes, blood glucose regulation
MeSH terms: Animals, Blood Glucose, Central Nervous System, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Humans, Hypoglycemia, Models, Biological, Neurosecretory Systems, Feedback, Physiological

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Neuroendocrine responses to hypoglycemia

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