Bile-induced secretion of glucagon-like peptide-1: pathophysiological implications in type 2 diabetes?
During the last decades it has become clear that bile acids not only act as simple fat solubilizers, but additionally represent complex hormonal metabolic integrators. Bile acids activate both nuclear receptors (controlling transcription of genes involved in for example bile acid, cholesterol, and glucose metabolism) and the cell surface G protein-coupled receptor TGR5 (modulating energy expenditure in brown fat and muscle cells). It has been shown that TGR5 is expressed in enteroendocrine L cells, which secrete the potent glucose-lowering incretin hormone glucagon-like peptide-1 (GLP-1). Recently it was shown that bile acid-induced activation of TGR5 results in intestinal secretion of GLP-1 and that enhanced TGR5 signaling improves postprandial glucose tolerance in diet-induced obese mice. This Perspectives article presents these novel findings in the context of prior studies on nutrient-induced GLP-1 secretion and outlines the potential implications of bile acid-induced GLP-1 secretion in physiological, pathophysiological, and pharmacological perspectives.
Knop
Filip K
FK
Department of Internal Medicine F, Gentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, Hellerup, Denmark. filipknop@dadlnet.dk
D000818:Animals; D001647:Bile Acids and Salts / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009765:Obesity / Q000503:physiopathology*; D019518:Postprandial Period / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology
D001647:Bile Acids and Salts; C473772:GPBAR1 protein, human; D043562:Receptors, G-Protein-Coupled; D052216:Glucagon-Like Peptide 1