Review
Version 1
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Is the β3-Adrenoceptor a Valid Target for the Treatment of Obesity and/or Type 2 Diabetes?
Version 1
: Received: 9 October 2023 / Approved: 10 October 2023 / Online: 11 October 2023 (14:22:08 CEST)
A peer-reviewed article of this Preprint also exists.
Dwaib, H.S.; Michel, M.C. Is the β3-Adrenoceptor a Valid Target for the Treatment of Obesity and/or Type 2 Diabetes? Biomolecules 2023, 13, 1714. Dwaib, H.S.; Michel, M.C. Is the β3-Adrenoceptor a Valid Target for the Treatment of Obesity and/or Type 2 Diabetes? Biomolecules 2023, 13, 1714.
Abstract
β3-Adrenoceptors mediate several functions in rodents that could be beneficial for the treatment of obesity and type 2 diabetes. This includes promotion of insulin release from the pancreas, of cellular glucose uptake, of lipolysis, and of thermogenesis in brown adipose tissue. In combination, they lead to a reduction of body weight in several rodent models including ob/ob mice and Zucker diabetic fatty rats. These findings stimulated drug development programs in various pharmaceutical companies, and at least nine β3-adrenoceptor agonists have been tested in clinical trials. However, all of these projects were discontinued due to lack of clinically relevant changes of body weight. Following a concise historical account of discoveries leading to such drug development programs we discuss species differences that explain why β3-adrenoceptors are not a meaningful drug target for the treatment of obesity and type 2 diabetes in humans.
Keywords
β3-adrenoceptor; obesity; type 2 diabetes; species difference; insulin release; glucose uptake; thermogenesis
Subject
Medicine and Pharmacology, Medicine and Pharmacology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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