The bile acid membrane receptor TGR5: a novel pharmacological target in metabolic, inflammatory and neoplastic disorders
MetadataShow full item record
TGR5 is the G-protein–coupled bile acid-activated receptor, found in many human and animal tissues. Considering different endocrine and paracrine functions of bile acids, the current review focuses on the role of TGR5 as a novel pharmacological target in the metabolic syndrome and related disorders, such as diabetes, obesity, atherosclerosis, liver diseases and cancer. TGR5 ligands improve insulin sensitivity and glucose homeostasis through the secretion of incretins. The bile acid/TGR5/cAMP signaling pathway increases energy expenditure in brown adipose tissue and skeletal muscle. Activation of TGR5 in macrophages inhibits production of proinflammatory cytokines and attenuates the development of atherosclerosis. This receptor has been detected in many cell types of the liver where it has anti-inflammatory effects, thus reducing liver steatosis and damage. TGR5 also modulates hepatic microcirculation and fluid secretion in the biliary tree. In cell culture models TGR5 has been linked to signaling pathways involved in metabolism, cell survival, proliferation and apoptosis, which suggest a possible role of TGR5 in cancer development. Despite the fact that TGR5 ligands may represent novel drugs for prevention and treatment of different aspects of the metabolic syndrome, clinical studies are awaited with the perspective that they will complete TGR5 biology and identify efficient and safe TGR5 agonists.
Showing items related by title, author, creator and subject.
Pharmacological effects of nanoencapsulation of human-based dosing of probucol on ratio of secondary to primary bile acids in gut, during induction and progression of type 1 diabetes.Mooranian, A.; Zamani, N.; Takechi, R.; Al-Sallami, H.; Mikov, M.; Golocorbin-Kon, S.; Kovacevic, B.; Arfuso, Frank; Al-Salami, H. (2018)INTRODUCTION: The ratio of secondary to primary bile acids changes during Type 1 Diabetes (T1D) development and these effects might be ameliorated by using cholesterol lowering drugs or hydrophilic bile acids. Probucol ...
Bile acids as novel pharmacological agents: The interplay between gene polymorphisms, epigenetic factors and drug responsePavlovic, N.; Stanimirov, Bojan; Mikov, Momir (2017)© 2017 Bentham Science Publishers. Background: The field of bile acid research has become tremendously active. Bile acids have been shown to act as signaling molecules that are involved in many metabolic processes, but ...
The roles of bile acids and applications of microencapsulation technology in treating Type 1 diabetes mellitusWoodhams, L.; Al-Salami, Hani (2017)Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the loss of glycemic control. Recent studies have shown significant inflammation and disturbed bile acid homeostasis, associated with T1DM. Bile ...