Obesity and type 2 diabetes are two concomitant metabolic disorders. Type 2 diabetes is a complex heterogeneous disease, and the number of patients continues to grow. Insulin resistance is a key cause of type 2 diabetes, and obesity is the main cause to produce insulin resistance.
For most patients with type 2 diabetes, insulin resistance and insulin secretion decrease exist simultaneously, which is the main pathophysiological mechanism.
G protein-coupled receptor with seven transmembrane ability is a common target for many therapeutic drugs. G protein-coupled receptors can affect insulin activity, insulin secretion and elongation of beta cells. Therefore, specific G protein-coupled receptors become potential drug targets for anti-diabetic therapy.
Insulin resistance
Leukotriene B4 (LTB4)
Free fatty acid receptor 4 (FFAR4)
Insulin secretion decrease
GLP1 receptor
It is generally believed that GLP1R agonists exert anti-diabetic effects mainly through three mechanisms:
1. GLP1R is abundantly expressed in pancreatic beta cells, and activation of GLP1 increases glucose stimulated insulin secretion (GSIS) based on the Gαs pathway.
2. GLP1 has an obvious inhibitory effect on glucagon secretion, which is an important component of GLP1R agonist in reducing blood glucose.
3. Moderate weight-loss caused by these drugs is beneficial to diabetes treatment.
FFAR1
The Glucose dependent-insulin receptor (GPR119)
CX3C chemokine receptor 1 (CX3CR1)
Summary and prospect
As a rapidly growing health care problem, diabetes has been increasing in morbidity and mortality, resulting in skyrocketing healthcare costs. Although there are some available anti-diabetic drugs, it is still difficult to achieve the ideal metabolic control for most patients. So it is necessary to find a more effective treatment, especially the new treatment based on the pathogenesis.
G protein-coupled receptor is a unique drug target for anti-diabetic treatment. At present, a large number of GLP1R-GLP1 have been used in the treatment, and some new GPCRs are also known as potential targets for drug research and development. Although FFAR1 and GPR119 study seems to have been weakened, the new FFAR1 plan is still in progress. Recently discovered new G protein-coupled receptors can affect insulin resistance or beta cell dysfunction, and its preclinical research is also very promising. In the aspect of anti-diabetic treatment, the method based on GPCR is still an active area to research and development at present.
More information about GPCR cell lines, please contact Creative Biogene.
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