Recently some researchers working in China Pharmaceutical

Recently, some researchers working in China Pharmaceutical University developed novel FFA1 agonists some of which were found to be efficacious in the management of type 2 diabetes and with low toxicity. For instance, Zheng et al. [48] in their in vivo study using experimental animals, reported that compound, 2- (4-[(2′-chloro-[1,1′-biphenyl]-3-yl) methoxy] phenyl) sulfonyl acetic acid, a phenylsulfonyl acetic Halopemide sale derivative demonstrated improved glucose tolerance in normal and type 2 diabetic models. The authors further reported that the compound showed a low risk of hypoglycemia in normal fasting rats even at high dose, a common adverse effect that arises from the use of sulfonylureas.
Potential beneficial role of FFAR1 in non beta-cell Whereas FFAR1 is mainly expressed in the pancreatic beta cells as earlier mentioned, it is also expressed in other tissues at comparatively lower levels such as the alpha cells of the pancreatic islets, where it is involved in regulating glucagon secretion in response to unsaturated FAs [49]. The expression of FFAR1 in the central nervous system is controversial. Whereas Itoh et al. [5] in their studies did not detect expression of GPR40 in the mouse brain; other studies reported FFAR1 expression in human, primate, rat and mouse brains [9,50] respectively. However, the functional role, of FFAR1 in the central nervous system remains unknown, although it has been shown to control pain regulatory systems [50]. Whereas data on experimental or clinical studies supporting the role of intra/extra cellular calcium management in the regulation and functions of FFAR1 is scarce in literature, there are indications that intra/extra cellular calcium management may play a role in the functions of FFAR1. This arises from studies that revealed that FFAR1 is also expressed in osteoclasts (function in breaking down bones to release calcium) and appears to mediate the inhibition of osteoclastogenesis by Fatty acid. Similar to these observations, Cornish et al. [51] observed that FFAR1 mice have reduced bone density. This raises the interesting possibility that FFAR1 agonism, besides improving glucose metabolism, might also protect against osteoporosis. This possibility, however, remains to be formally tested [52]. Finally, FFAR1 has been implicated in the stimulation of breast cancer cell line proliferation in response to oleate [53,54]. This suggests the possibility that chronic administration of GPR40 agonists might have undesirable effect, a possibility that obviously needs to be examined carefully.
Conclusion
Conflicts of interest
Type 2 diabetes is a major worldwide public health problem with devastating chronic complications such as cardiovascular disease, retinopathy, neuropathy, and nephropathy. Type 2 diabetes affects more than 300 million people globally and is predicted to become the seventh leading cause of death by 2030, with total deaths from diabetes projected to increase by 50% in the next 10years. The disease is polygenic in nature and characterized by hyperglycemia, defects in pancreatic insulin secretion, and insulin resistance in skeletal muscle, adipose tissue, and liver. In addition to these derangements, the rate of endogenous glucose production is significantly elevated in type 2 diabetics relative to healthy subjects., A variety of pharmacological strategies have been successfully employed to improve glycemic control in type 2 diabetics which directly target the secretion and sensitization of insulin. More recently, approaches targeting the endogenous antidiabetic hormone glucagon-like peptide-1 (GLP-1) have met with success. GLP-1, secreted from L-cells located in the ileum and colon, stimulates glucose-dependent insulin secretion and has been shown to inhibit glucagon release, gastric emptying, and feeding. GLP-1 (=2min) is rapidly degraded by the enzyme dipeptidylpeptidase-4 (DPP-4) and agents developed as long-acting agonists of GLP-1 (exenatide and liraglutide) and inhibitors of DPP-4 (sitagliptin and vildagliptin) have successfully validated GLP-1 as an important target for the development of new antidiabetic therapies.