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Diabetologia

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01-04-2019 | Carvedilol | Article

Carvedilol prevents counterregulatory failure and impaired hypoglycaemia awareness in non-diabetic recurrently hypoglycaemic rats

Authors: Rawad Farhat, Gong Su, Anne-Sophie Sejling, Nicholas Knight, Simon J. Fisher, Owen Chan

Published in: Diabetologia | Issue 4/2019

Abstract

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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Title: Carvedilol prevents counterregulatory failure and impaired hypoglycaemia awareness in non-diabetic recurrently hypoglycaemic rats
Authors: Rawad Farhat
Gong Su
Anne-Sophie Sejling
Nicholas Knight
Simon J. Fisher
Owen Chan
Publication date: 01-04-2019
Publisher: Springer Berlin Heidelberg
Keywords: Carvedilol
Insulins
Hypoglycemia
Insulins
Published in: Diabetologia / Issue 4/2019
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-018-4802-0

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