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.
|Number of pages||11|
|State||Published - Apr 1 2019|
Bibliographical noteFunding Information:
Funding The authors are grateful for the generosity of the agencies that helped fund this study: the JDRF (3-SRA-2017-487-S-B), the National Institutes of Health (R01 DK099315) and the University of Utah’s Diabetes and Metabolism Research Center. NK was supported by the Undergraduate Research Opportunities Program at the University of Utah.
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
- Counterregulatory failure
- Impaired hypoglycaemia awareness
- Recurrent hypoglycaemia
- Ventromedial hypothalamus (VMH)
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism