TY - JOUR

T1 - Postprandial gallbladder emptying in patients with type 2 diabetes

T2 - potential implications for bile-induced secretion of glucagon-like peptide 1

AU - Sonne, David P

AU - Rehfeld, Jens F

AU - Holst, Jens Juul

AU - Vilsbøll, Tina

AU - Knop, Filip K

N1 - © 2014 European Society of Endocrinology.

PY - 2014/10

Y1 - 2014/10

N2 - 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.DESIGN AND 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.

AB - 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.DESIGN AND 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.

KW - Adult

KW - Aged

KW - Area Under Curve

KW - Bile

KW - Biological Markers

KW - Blood Glucose

KW - C-Peptide

KW - Case-Control Studies

KW - Cholecystokinin

KW - Denmark

KW - Diabetes Mellitus, Type 2

KW - Dietary Fats

KW - Female

KW - Gallbladder Emptying

KW - Gastric Emptying

KW - Gastric Inhibitory Polypeptide

KW - Gastrins

KW - Glucagon

KW - Glucagon-Like Peptide 1

KW - Glucose Tolerance Test

KW - Humans

KW - Insulin

KW - Male

KW - Middle Aged

KW - Postprandial Period

KW - Receptors, G-Protein-Coupled

U2 - 10.1530/EJE-14-0309

DO - 10.1530/EJE-14-0309

M3 - Journal article

C2 - 24986531

VL - 171

SP - 407

EP - 419

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 4

ER -