title: Postprandial gallbladder emptying in patients with type 2 diabetes: potential implications for bile-induced secretion of glucagon-like peptide 1.
abstract: OBJECTIVE
  Recent preclinical work has suggested that postprandial flow of bile acids into the small intestine potentiates nutrient-induced glucagon-like peptide 1 (GLP1(GCG)) secretion via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells. The notion of bile-induced GLP1 secretion combined with the findings of reduced postprandial gallbladder emptying in patients with type 2 diabetes (T2DM) led us to speculate whether reduced postprandial GLP1 responses in some patients with T2DM arise as a consequence of diabetic gallbladder dysmotility.
  
  
  METHODS
  In a randomised design, 15 patients with long-standing T2DM and 15 healthy age-, gender- and BMI-matched control subjects were studied during 75-g oral glucose tolerance test (OGTT) and three isocaloric (500 kcal) and isovolaemic (350 ml) liquid meals: i) 2.5 g fat, 107 g carbohydrate and 13 g protein; ii) 10 g fat, 93 g carbohydrate and 11 g protein; and iii) 40 g fat, 32 g carbohydrate and 3 g protein. Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP1, glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin and gastrin were measured. Furthermore, gallbladder emptying and gastric emptying were examined.
  
  
  RESULTS
  Gallbladder emptying increased with increasing meal fat content, but no intergroup differences were demonstrated. GIP and GLP1 responses were comparable among the groups with GIP levels being higher following high-fat meals, whereas GLP1 secretion was similar after both OGTT and meals.
  
  
  CONCLUSIONS
  In conclusion, patients with T2DM exhibited normal gallbladder emptying to meals with a wide range of fat content. Incretin responses were similar to that in controls, and an association with postprandial gallbladder contraction could not be demonstrated.
authors.affiliation: Diabetes Research DivisionDepartment of Medicine, Gentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900 Hellerup, DenmarkThe NNF Center for Basic Metabolic ResearchDepartment of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, DenmarkDepartment of Clinical BiochemistryCopenhagen University Hospital Rigshospitalet, Copenhagen, Denmark Diabetes Research DivisionDepartment of Medicine, Gentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900 Hellerup, DenmarkThe NNF Center for Basic Metabolic ResearchDepartment of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, DenmarkDepartment of Clinical BiochemistryCopenhagen University Hospital Rigshospitalet, Copenhagen, Denmark dpsonne@gmail.com.
authors.forename: David P
authors.initials: DP
authors.lastname: Sonne
authors.affiliation: Diabetes Research DivisionDepartment of Medicine, Gentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900 Hellerup, DenmarkThe NNF Center for Basic Metabolic ResearchDepartment of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, DenmarkDepartment of Clinical BiochemistryCopenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jens F
authors.initials: JF
authors.lastname: Rehfeld
authors.affiliation: Diabetes Research DivisionDepartment of Medicine, Gentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900 Hellerup, DenmarkThe NNF Center for Basic Metabolic ResearchDepartment of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, DenmarkDepartment of Clinical BiochemistryCopenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Diabetes Research DivisionDepartment of Medicine, Gentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900 Hellerup, DenmarkThe NNF Center for Basic Metabolic ResearchDepartment of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, DenmarkDepartment of Clinical BiochemistryCopenhagen University Hospital Rigshospitalet, Copenhagen, Denmark Diabetes Research DivisionDepartment of Medicine, Gentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900 Hellerup, DenmarkThe NNF Center for Basic Metabolic ResearchDepartment of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, DenmarkDepartment of Clinical BiochemistryCopenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
authors.affiliation: Diabetes Research DivisionDepartment of Medicine, Gentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900 Hellerup, DenmarkThe NNF Center for Basic Metabolic ResearchDepartment of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, DenmarkDepartment of Clinical BiochemistryCopenhagen University Hospital Rigshospitalet, Copenhagen, Denmark Diabetes Research DivisionDepartment of Medicine, Gentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900 Hellerup, DenmarkThe NNF Center for Basic Metabolic ResearchDepartment of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, DenmarkDepartment of Clinical BiochemistryCopenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001646:Bile / Q000378:metabolism; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D002766:Cholecystokinin / Q000097:blood; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage*; D005260:Female; D016473:Gallbladder Emptying; D005746:Gastric Emptying; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005755:Gastrins / Q000097:blood; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood* / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D043562:Receptors, G-Protein-Coupled / Q000097:blood
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D004041:Dietary Fats; C473772:GPBAR1 protein, human; D005755:Gastrins; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D002766:Cholecystokinin