» Articles » PMID: 33855225

Carvedilol Prevents Impairment of the Counterregulatory Response in Recurrently Hypoglycaemic Diabetic Rats

Overview
Specialty Endocrinology
Date 2021 Apr 15
PMID 33855225
Citations 4
Authors
Affiliations
Soon will be listed here.
Abstract

Aim: It has been suggested that repeated activation of the adrenergic system during antecedent episodes of hypoglycaemia contributes to the development of counterregulatory failure. We previously reported that treatment with carvedilol, a non-specific β-blocker, prevented the development of counterregulatory failure and improved hypoglycaemia awareness in recurrently hypoglycaemic non-diabetic rats. The current study investigated whether carvedilol has similar benefits in diabetic rats.

Methods: Recurrently hypoglycaemic streptozotocin-diabetic rats (STZ+RH) were treated with carvedilol for one week prior to undergoing a hypoglycaemic clamp. Hypoglycaemia awareness was evaluated in streptozotocin-diabetic rats made hypoglycaemia unaware using repeated injections of 2-deoxyglucose.

Results: Compared to hypoglycaemia-naïve STZ-diabetic controls, exogenous glucose requirements were more than doubled in the STZ+RH animals and this was associated with a 49% reduction in the epinephrine response to hypoglycaemia. Treating STZ+RH animals with carvedilol improved the epinephrine response to hypoglycaemia. Of note, neither recurrent hypoglycaemia nor carvedilol treatment affected the glucagon response in diabetic animals. Additionally, carvedilol treatment improved the feeding response to insulin-induced hypoglycaemia in diabetic animals made 'hypoglycaemia unaware' using repeated injections of 2-deoxyglucose, suggesting the treatment improved awareness of hypoglycaemia as well.

Conclusion: Our data suggest that carvedilol may be useful in preventing impairments of the sympathoadrenal response and the development of hypoglycaemia unawareness during recurring episodes of hypoglycaemia in diabetic animals.

Citing Articles

Glucagon-like peptide-1 and impaired counterregulatory responses to hypoglycemia in type 1 diabetes.

Rocha G, de Melo F World J Diabetes. 2025; 16(2):99928.

PMID: 39959274 PMC: 11718485. DOI: 10.4239/wjd.v16.i2.99928.


Role of the Adrenal Medulla in Hypoglycaemia-Associated Autonomic Failure-A Diabetic Perspective.

Senthilkumaran M, Koch C, Herselman M, Bobrovskaya L Metabolites. 2024; 14(2).

PMID: 38392992 PMC: 10890365. DOI: 10.3390/metabo14020100.


Experimental pharmacological approaches to reverse impaired awareness of hypoglycemia-a review.

Hashmi H, Khowaja A, Moheet A Front Pharmacol. 2024; 15:1349004.

PMID: 38323079 PMC: 10844401. DOI: 10.3389/fphar.2024.1349004.


Current and future therapies to treat impaired awareness of hypoglycemia.

Macon E, Devore M, Lin Y, Music M, Wooten M, McMullen C Front Pharmacol. 2023; 14:1271814.

PMID: 37942482 PMC: 10628050. DOI: 10.3389/fphar.2023.1271814.


Effects of Carvedilol on Blood Pressure, Blood Sugar, and Blood Lipids in Elderly Patients with Refractory Hypertension.

Zhang W, Deng G, Hu J, Yan R, Hu J, Fan J Comput Math Methods Med. 2022; 2022:7889024.

PMID: 35936366 PMC: 9348927. DOI: 10.1155/2022/7889024.

References
1.
Zhu W, Czyzyk D, Paranjape S, Zhou L, Horblitt A, Szabo G . Glucose prevents the fall in ventromedial hypothalamic GABA that is required for full activation of glucose counterregulatory responses during hypoglycemia. Am J Physiol Endocrinol Metab. 2010; 298(5):E971-7. PMC: 2867375. DOI: 10.1152/ajpendo.00749.2009. View

2.
Taborsky Jr G, Ahren B, Mundinger T, Mei Q, Havel P . Autonomic mechanism and defects in the glucagon response to insulin-induced hypoglycaemia. Diabetes Nutr Metab. 2003; 15(5):318-22; discussion 322-3. View

3.
Chan O, Paranjape S, Czyzyk D, Horblitt A, Zhu W, Ding Y . Increased GABAergic output in the ventromedial hypothalamus contributes to impaired hypoglycemic counterregulation in diabetic rats. Diabetes. 2011; 60(5):1582-9. PMC: 3292334. DOI: 10.2337/db10-1579. View

4.
Fan X, Ding Y, Brown S, Zhou L, Shaw M, Vella M . Hypothalamic AMP-activated protein kinase activation with AICAR amplifies counterregulatory responses to hypoglycemia in a rodent model of type 1 diabetes. Am J Physiol Regul Integr Comp Physiol. 2009; 296(6):R1702-8. PMC: 2692788. DOI: 10.1152/ajpregu.90600.2008. View

5.
Lo Y, Lynch S, Urbanowicz R, Olson R, Ritter A, Whitehouse C . Using Machine Learning on Home Health Care Assessments to Predict Fall Risk. Stud Health Technol Inform. 2019; 264:684-688. DOI: 10.3233/SHTI190310. View