RESUMO
Bile acids (BAs), the end products of cholesterol catabolism, are essential for the absorption of lipids and fat-soluble vitamins; but they have also emerged as novel signaling molecules that act as metabolic regulators. It has been well described that the enterohepatic circulation, a nuclear (FXR) and a cytoplasmic (TGR5/M-BAR) receptor aid in controlling hepatic bile acid synthesis. Modulating bile acid synthesis greatly impacts in metabolism, because these receptors also are implicated in glucose, lipid, and energy expenditure. Recent studies had revealed the way these receptors participate in regulating gluconeogenesis, peripheral insulin sensitivity, glycogen synthesis, glucagon like peptide 1 (GLP-1) and insulin secretion. Nowadays, it is demonstrated that enhancing bile acid signaling in the intestine contributes to the metabolic benefits of bile acid sequestrants and bariatric surgery on glucose homeostasis. This paper discusses the role of bile acid as regulators of glucose metabolism and their potential as therapeutic targets for diabetes.
Assuntos
Ácidos e Sais Biliares/metabolismo , Glicemia/metabolismo , Diabetes Mellitus/metabolismo , Mucosa Intestinal/metabolismo , Fígado/metabolismo , Animais , Ácidos e Sais Biliares/sangue , Glicemia/efeitos dos fármacos , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Metabolismo Energético , Humanos , Hipoglicemiantes/uso terapêutico , Intestinos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transdução de SinaisRESUMO
Bile acids (BAs), the end products of cholesterol catabolism, are essential for the absorption of lipids and fat-soluble vitamins; but they have also emerged as novel signaling molecules that act as metabolic regulators. It has been well described that the enterohe-patic circulation, a nuclear (FXR) and a cytoplasmic (TGR5/M-BAR) receptor aid in controlling hepatic bile acid synthesis. Modulating bile acid synthesis greatly impacts in metabolism, because these receptors also are implicated in glucose, lipid, and energy expenditure. Recent studies had revealed the way these receptors participate in regulating gluconeogenesis, peripheral insulin sensitivity, glycogen synthesis, glucagon like peptide 1 (GLP-1) and insulin secretion. Nowadays, it is demonstrated that enhancing bile acid signaling in the intestine contributes to the metabolic benefits of bile acid sequestrants and bariatric surgery on glucose homeos-tasis. This paper discusses the role of bile acid as regulators of glucose metabolism and their potential as therapeutic targets for diabetes.