TY - JOUR
T1 - Targeting appetite and satiety in diabetes and obesity, via G protein-coupled receptors
AU - Piper, Noah B.C.
AU - Whitfield, Emily A.
AU - Stewart, Gregory D.
AU - Xu, Xiaomeng
AU - Furness, Sebastian G.B.
N1 - Funding Information:
This work is supported by funding from the Faculty of Medicine, University of Queensland and NHMRC Ideas grant APP2012657 . S.G.B.F is an ARC Future Fellow (FT180100543), N.B.C.P. and E.A.W. are recipients of Australian Government Research Training Scholarships.
Funding Information:
This work is supported by funding from the Faculty of Medicine, University of Queensland and NHMRC Ideas grant APP2012657. S.G.B.F is an ARC Future Fellow (FT180100543), N.B.C.P. and E.A.W. are recipients of Australian Government Research Training Scholarships.
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/8
Y1 - 2022/8
N2 - Type 2 diabetes and obesity have reached pandemic proportions throughout the world, so much so that the World Health Organisation coined the term “Globesity” to help encapsulate the magnitude of the problem. G protein-coupled receptors (GPCRs) are highly tractable drug targets due to their wide involvement in all aspects of physiology and pathophysiology, indeed, GPCRs are the targets of approximately 30% of the currently approved drugs. GPCRs are also broadly involved in key physiologies that underlie type 2 diabetes and obesity including feeding reward, appetite and satiety, regulation of blood glucose levels, energy homeostasis and adipose function. Despite this, only two GPCRs are the target of approved pharmaceuticals for treatment of type 2 diabetes and obesity. In this review we discuss the role of these, and select other candidate GPCRs, involved in various facets of type 2 diabetic or obese pathophysiology, how they might be targeted and the potential reasons why pharmaceuticals against these targets have not progressed to clinical use. Finally, we provide a perspective on the current development pipeline of anti-obesity drugs that target GPCRs.
AB - Type 2 diabetes and obesity have reached pandemic proportions throughout the world, so much so that the World Health Organisation coined the term “Globesity” to help encapsulate the magnitude of the problem. G protein-coupled receptors (GPCRs) are highly tractable drug targets due to their wide involvement in all aspects of physiology and pathophysiology, indeed, GPCRs are the targets of approximately 30% of the currently approved drugs. GPCRs are also broadly involved in key physiologies that underlie type 2 diabetes and obesity including feeding reward, appetite and satiety, regulation of blood glucose levels, energy homeostasis and adipose function. Despite this, only two GPCRs are the target of approved pharmaceuticals for treatment of type 2 diabetes and obesity. In this review we discuss the role of these, and select other candidate GPCRs, involved in various facets of type 2 diabetic or obese pathophysiology, how they might be targeted and the potential reasons why pharmaceuticals against these targets have not progressed to clinical use. Finally, we provide a perspective on the current development pipeline of anti-obesity drugs that target GPCRs.
KW - Appetite
KW - Diabetes
KW - GPCR
KW - Obesity
KW - Review
KW - Satiety
UR - http://www.scopus.com/inward/record.url?scp=85131946647&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2022.115115
DO - 10.1016/j.bcp.2022.115115
M3 - Review Article
C2 - 35671790
AN - SCOPUS:85131946647
SN - 0006-2952
VL - 202
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
M1 - 115115
ER -
