Neural and Cardiac Responses to Hypoglycemia

Update item information
Identifier neural_cardiac_responses_hypoglycemia
Title Neural and Cardiac Responses to Hypoglycemia
Creator Fisher, S.; Chan, O.; Reno, C.; Internal Medicine; School of Medicine; University of Utah Health
Keyword Diabetes and Metabolism
Image Caption Over-treatment with insulin leads to hypoglycemia that results in the release of the neurotransmitter glutamate in the brain which enhances autonomic nervous system output. Increased autonomic output to the heart and other organs help raise blood glucose levels. Extreme hypoglycemia, however, causes excessive activation of both sympathetic and parasympathetic branches of the autonomic nervous system which can lead to fatal cardiac arrhythmias.
Description In the setting of insulin therapy, patients with Type 1 diabetes (T1D) are at particularly high risk for hypoglycemia (low blood sugar) because of an impaired ability of the brain to sense and respond appropriately to hypoglycemia. The physiologic basis of this impairment is, however, unclear. The laboratories of Simon Fisher, MD, Owen Chan, PhD, and Candace Reno, PhD, demonstrated that brain glucose sensing was impaired in rats with recurrent hypoglycemia as a result of defective glucose and lactate metabolism within the neurons and astrocytes in the hypothalamus. The resultant abnormal release of neurotransmitters-such as GABA, glutamate and dopamine-led to inadequate activation of hormonal responses to hypoglycemia. This detrimental effect, however, could be prevented by treatment with the beta-blocker carvedilol in rats. They further demonstrated that severe hypoglycemia led to coma, brain damage and fatal cardiac arrhythmias, and these effects were mediated by excessive activation of the autonomic nervous system. Based on these results, the investigators have launched a clinical trial to examine the efficacy of the drug metoclopramide to restore the neurotransmitter and hormonal responses and awareness to hypoglycemia in people with T1D.
Relation is Part of 2017
Publisher Spencer S. Eccles Health Sciences Library, University of Utah
Date Digital 2021
Date 2017
Type Image
Format image/jpeg
Rights Management Copyright © 2021, University of Utah, All Rights Reserved
Language eng
ARK ark:/87278/s6nd214h
References 1.) Brain glut4 knockout mice have impaired glucose tolerance, decreased insulin sensitivity, and impaired hypoglycemic counterregulation. Reno CM, Puente EC, Sheng Z, Daphna-Iken D, Bree AJ, Routh VH, Kahn BB, Fisher SJ. Diabetes. 2017 March;66(3):587. 2.) Impaired glutamatergic neurotransmission in the ventromedial hypothalamus may contribute to defective counterregulation in recurrently hypoglycemic rats. Chowdhury GMI, Wang P, Ciardi A, Mamillapalli R, Johnson J, Zhu W, Eid T, Behar, Chan O. Diabetes. 2017 July;66(7):1979. 3.) Severe Hypoglycemia-Induced Fatal Cardiac Arrhythmias Are Augmented by Diabetes and Attenuated by Recurrent Hypoglycemia. Reno CM, VanderWeele J, Bayles J, Litvin M, Skinner A, Jordan A, Daphna-Iken D, Fisher S. Diabetes. 2017 December;66(12):3091. 4.) Prevention of severe hypoglycemia-induced brain damage and cognitive impairment with verapamil. Jackson DA, Michael T, Vieira de Abreu A, Agarwal R, Bortolato M, Fisher SJ. Diabetes. 2018 October;67(10):2107. 5.) Carvedilol prevents counterregulatory failure and impaired hypoglycaemia awareness in sprague-dawley rats. Farhat R, Su G, Sejling AS, Knight N, Fisher SJ, Chan O. Diabetologia. 2019 April;62(4):676. 6.) Severe hypoglycemia-induced fatal cardiac arrhythmias are mediated by the parasympathetic nervous system in rats. Reno CM, Bayles J, Huang Y, Oxspring M, Hirahara AM, Dosdall DJ, Fisher SJ. Diabetes. 2019 November;68(11):2107.
Setname ehsl_50disc
Date Created 2021-06-22
Date Modified 2021-06-25
ID 1703453
Reference URL