Metabolic roles of G protein-coupled receptor signaling in obesity and type 2 diabetes
- PMID: 33682344
- DOI: 10.1111/febs.15800
Metabolic roles of G protein-coupled receptor signaling in obesity and type 2 diabetes
Abstract
The incidence of obesity and type 2 diabetes (T2D) has been increasing steadily worldwide. It is estimated that by 2045 more than 800 million people will be suffering from diabetes. Despite the advancements in modern medicine, more effective therapies for treating obesity and T2D are needed. G protein-coupled receptors (GPCRs) have emerged as important drug targets for various chronic diseases, including obesity, T2D, and liver diseases. During the past two decades, many laboratories worldwide focused on understanding the role of GPCR signaling in regulating glucose metabolism and energy homeostasis. The information gained from these studies can guide the development of novel therapeutic agents. In this review, we summarize recent studies providing insights into the role of GPCR signaling in peripheral, metabolically important tissues such as pancreas, liver, skeletal muscle, and adipose tissue, focusing primarily on the use of mutant animal models and human data.
Keywords: G protein-coupled receptors; chronic diseases and glucose homeostasis; drug discovery; metabolism; nonalcoholic fatty liver disease; obesity; type 2 diabetes.
© 2021 Federation of European Biochemical Societies.
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References
-
- Meldrum DR, Morris MA & Gambone JC (2017) Obesity pandemic: causes, consequences, and solutions-but do we have the will? Fertil Steril 107, 833-839.
-
- Roden M & Shulman GI (2019) The integrative biology of type 2 diabetes. Nature 576, 51-60.
-
- Mahajan A, Wessel J, Willems SM, Zhao W, Robertson NR, Chu AY, Gan W, Kitajima H, Taliun D, Rayner NW et al. (2018) Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes. Nat Genet 50, 559-571.
-
- Centers for Disease Control and Prevention (2020) National Diabetes Statistics Report. Estimates of diabetes and Its burden in the United States.
-
- Wang L, Pydi SP, Zhu L, Barella LF, Cui Y, Gavrilova O, Bence KK, Vernochet C & Wess J (2020) Adipocyte Gi signaling is essential for maintaining whole-body glucose homeostasis and insulin sensitivity. Nat Commun 11, 2995.
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