title: Investigating the effects of physiological bile acids on GLP-1 secretion and glucose tolerance in normal and GLP-1R(-/-) mice.
abstract: Physiological secretion of bile acids has previously been linked to the regulation of blood glucose. GLP-1 is an intestinal peptide hormone with important glucose-lowering actions, such as stimulation of insulin secretion and inhibition of glucagon secretion. In this investigation, we assessed the ability of several bile acid compounds to secrete GLP-1 in vitro in STC-1 cells. Bile acids stimulated GLP-1 secretion from 3.3- to 6.2-fold but some were associated with cytolytic effects. Glycocholic and taurocholic acids were selected for in vivo studies in normal and GLP-1R(-/-) mice. Oral glucose tolerance tests revealed that glycocholic acid did not affect glucose excursions. However, taurocholic acid reduced glucose excursions by 40% in normal mice and by 27% in GLP-1R(-/-) mice, and plasma GLP-1 concentrations were significantly elevated 30 min post-gavage. Additional studies used incretin receptor antagonists to probe involvement of GLP-1 and GIP in taurocholic acid-induced glucose lowering. The findings suggest that bile acids partially aid glucose regulation by physiologically enhancing nutrient-induced GLP-1 secretion. However, GLP-1 secretion appears to be only part of the glucose-lowering mechanism and our studies indicate that the other major incretin GIP is not involved.
authors.affiliation: School of Biological Sciences, Queen's University Belfast, BT9 5AG, UK.
authors.forename: Eamon P
authors.initials: EP
authors.lastname: Rafferty
authors.forename: Alastair R
authors.initials: AR
authors.lastname: Wylie
authors.forename: Katharine H
authors.initials: KH
authors.lastname: Hand
authors.forename: Chris E
authors.initials: CE
authors.lastname: Elliott
authors.forename: David J
authors.initials: DJ
authors.lastname: Grieve
authors.forename: Brian D
authors.initials: BD
authors.lastname: Green
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D000067757:Glucagon-Like Peptide-1 Receptor; D018149:Glucose Intolerance / Q000378:metabolism*; D005951:Glucose Tolerance Test; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008968:Molecular Conformation; D018027:Receptors, Glucagon / Q000172:deficiency* / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D001647:Bile Acids and Salts; D001786:Blood Glucose; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon