Carvedilol prevents counterregulatory failure and impaired hypoglycaemia awareness in non-diabetic recurrently hypoglycaemic rats
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Aims/hypothesis This study evaluates whether the non-selective β-blocker, carvedilol, can be used to prevent counterregulatory failure and the development of impaired awareness of hypoglycaemia (IAH) in recurrently hypoglycaemic rats.Methods Sprague Dawley rats were implanted with vascular catheters and intracranial guide cannulas targeting the ventromedial hypothalamus (VMH). These animals underwent either three bouts of insulin-induced hypoglycaemia or received three saline injections (control group) over 3 days. A subgroup of recurrently hypoglycaemic animals was treated with carvedilol. The next day, the animals underwent a hypoglycaemic clamp with microdialysis without carvedilol treatment to evaluate changes in central lactate and hormone levels. To assess whether carvedilol prevented IAH, we treated rats that had received repeated 2-deoxyglucose (2DG) injections to impair their awareness of hypoglycaemia with carvedilol and measured food intake in response to insulin-induced hypoglycaemia as a surrogate marker for hypoglycaemia awareness.Results Compared with the control group, recurrently hypoglycaemic rats had a ~1.7-fold increase in VMH lactate and this was associated with a 75% reduction in the sympathoadrenal response to hypoglycaemia. Treatment with carvedilol restored VMH lactate levels and improved the adrenaline (epinephrine) responses. In 2DG-treated rats compared with control animals receiving saline, food intake was reduced in response to hypoglycaemia and increased with carvedilol treatment.Conclusions/interpretation We conclude that carvedilol may be a useful therapy to prevent counterregulatory failure and improve IAH.
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Administration of the nonselective beta blocker carvedilol during antecedent hypoglycemia in rats preserved hypoglycemia awareness and counter-regulatory hormone responses to a subsequent hypoglycemic challenge.
“administration of the nonselective beta blocker carvedilol during antecedent hypoglycemia in rats preserved hypoglycemia awareness and counter-regulatory hormone responses to a subsequent hypoglycemic challenge (32).”
From Plasma Epinephrine Contributes to the Development of Experimental Hypoglycemia-Associated Autonomic Failure (2020) · cites this paper as [32]
The Results (‘Hormone response with recurrent hypoglycaemia’; page not provided) report that carvedilol fully restored the adrenaline response to a subsequent hypoglycaemic challenge, but its improvement of glucagon responses was not statistically significant. Awareness was assessed separately after repeated 2-deoxyglucose injections, not antecedent insulin-induced hypoglycaemia, using food intake as a surrogate (Methods, ‘Study 3’; Discussion; pages not provided). (LLM, conf=0.88)
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- Authors
- Farhat, R., Su, G., Sejling, A.-S., Knight, N., Fisher, S. J., & Chan, O.
- Affiliations
- University of Utah (US)
- Capital Medical University (CN)
- Novo Nordisk (Denmark) (DK)
- Corresponding author
- Chan, Owen
- Venue
- Diabetologia
- Published
- 2019-01-09
- Volume
- 62
- Issue
- 4
- Pages
- 676-686
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC6403018
- OpenAlex
- W2909500627
- Cited by
- 12
- References
- 57
- Citations by year
- 2026: 1 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 1
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Juvenile Diabetes Research Foundation International (3-SRA-2017-487-S-B)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK099315)
- 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
- carvedilol, impaired awareness of hypoglycaemia, recurrent hypoglycemia, beta-blockers, ventromedial hypothalamus, lactate, sympathoadrenal response, epinephrine, insulin-induced hypoglycemia, 2-deoxyglucose, dietary intake
- MeSH terms
- Carvedilol, Animals, Blood Glucose, Body Weight, Catheterization, Deoxyglucose, Disease Models, Animal, Hyperglycemia, Hypoglycemia, Hypoglycemic Agents, Insulin, Male, Recurrence, Time Factors, Ventromedial Hypothalamic Nucleus, Glucose Clamp Technique, Rats, Sprague-Dawley, Lactic Acid, Rats, Adrenergic beta-1 Receptor Antagonists
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