Our promise to you:
Guaranteed product quality, expert customer support.


The Applications of G Protein Coupled Receptor (GPCR) in Antidiabetic Drug Research and Development

Diabetes is a disease that seriously threatens human health, and type 2 diabetes makes up about 90% of cases of diabetes[1]. Type 2 diabetes is a long-term metabolic disorder that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Type 2 diabetes primarily occurs as a result of obesity and lack of exercise. In recent years, the treatment of type 2 diabetes has been mainly focused on promoting insulin secretion and controlling blood sugar levels by regulating glucose metabolism pathway, such as glucagon like peptide -1 (GLP-1) analog and dipeptidyl peptidase-iv (DPP-4) inhibitors. In addition, there are some compounds that can promote the secretion of insulin through binding with the G protein coupled receptor (GPCR) , to achieve the purpose of treating type 2 diabetes.

GPCRs are membrane-bound proteins that have seven membrane-spanning domains connected by intracellular and extracellular domains. GPCRs act as receptors for a multitude of different signals. They are involved in numerous physiological processes, including the regulation of neuronal excitability, metabolism, reproduction, development, hormonal homeostasis, and behavior[2]. Diverse members of the GPCR super family participate in a variety of physiological functions and are major targets of pharmaceutical drugs. GPCRs can affect insulin activity, insulin secretion and elongation of β cells. Therefore, specific GPCRs have become potential targets for antidiabetic therapy.


GLP-1 is one of the key incretin hormones secreted in response to food intake and gastric motility, and is responsible for glucose homeostasis via the stimulation of insulin secretion through activation of GLP-1R[3]. The treatment of type 2 diabetes requires positive modulation of GLP-1R to inhibit glucagon secretion and stimulate insulin secretion in a glucose-dependent manner2. And peptide analogues of GLP-1 have been successfully developed for the treatment of type 2 diabetes[4]. Recently, Chinese researches have solved structures of the human GLP-1R TMD in complex with two negative allosteric modulators (NAMs), and complemented these structures with mutagenesis and modelling studies to map the binding site[5]. These findings provide important clues for the development of therapeutically viable non-peptidic GLP-1R agonists.


GPR40, also known as, free fatty acid receptor 1 (FFA1), is encoded by the FFAR1 gene. This membrane protein binds free fatty acids, acting as a nutrient sensor for regulating energy homeostasis. GPR40 could strengthen the function of islet β cells, promote insulin secretion and improve the body's sensitivity to insulin through activating GPCRs , so as to achieve the goal of treating diabetes. So GPR40 agonists and/or antagonists show potential for the development of new anti-diabetic drugs[6].


GPR119 a member of the rhodopsin subfamily of G-protein-coupled receptors that is expressed in the pancreas and gastrointestinal tract. The encoded protein is activated by lipid amides including lysophosphatidylcholine and oleoylethanolamide. GPR119 agonists increase intracelluar cAMP levels, leading to enhanced glucose-dependent insulin release and glucagon like peptide (GLP1) secretion, decreased blood glucose level, and preserve pancreatic βcells function, which in combination improve the systemic glucose homeostasis. Thus GPR119 is used as a promising target for development of type 2 diabetes therapeutic drugs.


GPR120, a novel FFA receptor, can directly or indirectly regulate a series of in vivo metabolic processes, such as hormone secretion, glucose metabolism, signal transduction. GPR120 as a potential therapeutic target for different metabolic diseases. And studies have found that GPR120 can bind fatty acid hydroxy fatty acids (FAHFAs), so as to control the amount of glucose that is absorbed into fat cells. So there may also be a pathway to treat or prevent diabetes by increasing FAHFAs levels and activating GPR120.

Conclusion and Expectation

GPCRs is a unique drug target for the treatment of diabetes. A large number of GLP1R-GLP1 have been used in the treatment, and some new GPCRs are also referred to as potential targets for drug research and development. While the early research heat of FFAR1 and GPR119 seems to have waned, the new project of FFAR1 is still in process. Peptide analogues of GLP-1 have beensuccessfully developed for the treatment of type 2 diabetes2, but the development of therapeutically viable non-peptidic GLP-1R agonists has been unsuccessful. So GPR40 is as a target for antidiabetic drugs, where many problems can be studied further.


  1. Wild S, Roglic G, Green A, et al. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030[J]. Diabetes Care, 2004, 27(5): 1047-1053.
  2. Vassilatis D K, Hohmann J G, Zeng H, et al. The G protein-coupled receptor repertoires of human and mouse[J]. Proc Natl Acad Sci U S A, 2003, 100(8): 4903-4908.
  3. Cd G, Donnelly D, Wootten D, et al. Glucagon-like peptide-1 and its class B G protein-coupled receptors: a long march to therapeutic successes[J]. Pharmacological Reviews, 2016, 68(4):954.
  4. Cho Y M, Merchant C E, Kieffer T J. Targeting the glucagon receptor family for diabetes and obesity therapy[J]. Pharmacology & Therapeutics, 2012, 135(3):247.
  5. Song G, Yang D, Wang Y, et al. Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators.[J]. Nature, 2017, 546(7657):312.
  6. Itoh Y, Kawamata Y, Harada M, et al. Free fatty acids regulate insulin secretion from pancreatic cells through GPR40. Nature, 2003, 422(6928):173-176.
For research use only. Not intended for any clinical use.

Quick Inquiry

Verification code