机构：[1]Division of Endocrinology,Metabolism and Diabetes, Department of Internal Medicine, University of Utah, Department 15 North 2030 East, EIHG Building 533, Room 2420B, Salt Lake City, UT 84112, USA[2]Beijing An Zhen Hospital, Capital Medical University, Beijing, China首都医科大学附属安贞医院[3]Novo-Nordisk A/S, Søborg, Denmark
Aims/hypothesisThis study evaluates whether the non-selective -blocker, carvedilol, can be used to prevent counterregulatory failure and the development of impaired awareness of hypoglycaemia (IAH) in recurrently hypoglycaemic rats.MethodsSprague 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 3days. 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.ResultsCompared with the control group, recurrently hypoglycaemic rats had a similar to 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/interpretationWe conclude that carvedilol may be a useful therapy to prevent counterregulatory failure and improve IAH.
基金：
JDRFJuvenile Diabetes Research Foundation [3-SRA-2017-487-S-B]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 DK099315]; University of Utah's Diabetes and Metabolism Research Center; Undergraduate Research Opportunities Program at the University of Utah
第一作者机构：[1]Division of Endocrinology,Metabolism and Diabetes, Department of Internal Medicine, University of Utah, Department 15 North 2030 East, EIHG Building 533, Room 2420B, Salt Lake City, UT 84112, USA
通讯作者：
通讯机构：[1]Division of Endocrinology,Metabolism and Diabetes, Department of Internal Medicine, University of Utah, Department 15 North 2030 East, EIHG Building 533, Room 2420B, Salt Lake City, UT 84112, USA
推荐引用方式(GB/T 7714)：
Rawad Farhat,Gong Su,Anne-Sophie Sejling,et al.Carvedilol prevents counterregulatory failure and impaired hypoglycaemia awareness in non-diabetic recurrently hypoglycaemic rats[J].DIABETOLOGIA.2019,62(4):676-686.doi:10.1007/s00125-018-4802-0.
APA：
Rawad Farhat,Gong Su,Anne-Sophie Sejling,Nicholas Knight,Simon J. Fisher&Owen Chan.(2019).Carvedilol prevents counterregulatory failure and impaired hypoglycaemia awareness in non-diabetic recurrently hypoglycaemic rats.DIABETOLOGIA,62,(4)
MLA：
Rawad Farhat,et al."Carvedilol prevents counterregulatory failure and impaired hypoglycaemia awareness in non-diabetic recurrently hypoglycaemic rats".DIABETOLOGIA 62..4(2019):676-686
医学