Investigating the effects of physiological bile acids on GLP-1 secretion and glucose tolerance in normal and GLP-1R(-/-) mice

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 a...

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Bibliographic Details
Published in:	Biological chemistry Vol. 392; no. 6; p. 539
Main Authors:	Rafferty, Eamon P, Wylie, Alastair R, Hand, Katharine H, Elliott, Chris E, Grieve, David J, Green, Brian D
Format:	Journal Article
Language:	English
Published:	Germany 01-04-2011
Subjects:	Animals Bile Acids and Salts - pharmacology Blood Glucose - drug effects Blood Glucose - metabolism Cells, Cultured Glucagon-Like Peptide-1 Receptor Glucose Intolerance - metabolism Glucose Tolerance Test Mice Mice, Inbred C57BL Mice, Knockout Molecular Conformation Receptors, Glucagon - deficiency Receptors, Glucagon - metabolism Stereoisomerism
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Summary:	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.
ISSN:	1437-4315
DOI:	10.1515/bc.2011.050