Rectal taurocholate increases L cell and insulin secretion, and decreases blood glucose and food intake in obese type 2 diabetic volunteers.
OBJECTIVE
Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are secreted from enteroendocrine L cells in response to numerous stimuli, including bile salts. Both have multiple effects that are potentially useful in treating diabetes and obesity. L cell number and hormone content in the intestine are highest in the rectum in humans. We investigated the effects of intrarectal sodium taurocholate on plasma GLP-1, PYY, insulin and glucose concentrations, and on food intake of a subsequent meal.


METHODS
Ten obese type 2 diabetic volunteers were each studied on five separate occasions after an overnight fast and oral administration of 100 mg sitagliptin 10 h before the study. They then received an intrarectal infusion of either one of four doses of taurocholate (0.66, 2, 6.66 or 20 mmol, each in 20 ml of vehicle) or vehicle alone (1% carboxymethyl cellulose) single-blind over 1 min. Hormone and glucose measurements were made prior to, and for 1 h following, the infusion. The consumption of a previously selected favourite meal eaten to satiety was measured 75 min after the infusion.


RESULTS
Taurocholate dose-dependently increased GLP-1, PYY and insulin, with 20 mmol doses resulting in peak concentrations 7.2-, 4.2- and 2.6-fold higher, respectively, than those achieved with placebo (p < 0.0001 for each). Plasma glucose decreased by up to 3.8 mmol/l (p < 0.001). Energy intake was decreased dose-dependently by up to 47% (p < 0.0001). The ED(50) values for effects on integrated GLP-1, insulin, PYY, food intake and glucose-lowering responses were 8.1, 10.5, 18.5, 24.2 and 25.1 mmol, respectively.


CONCLUSIONS
Therapies that increase bile salts (or their mimics) in the distal bowel may be valuable in the treatment of type 2 diabetes and obesity.
Department of Physiology, Faculty of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates. tadrian@uaeu.ac.ae
T E
TE
Adrian
S
S
Gariballa
K A
KA
Parekh
S A
SA
Thomas
H
H
Saadi
J
J
Al Kaabi
N
N
Nagelkerke
B
B
Gedulin
A A
AA
Young
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004435:Eating; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000378:metabolism; D019894:Peptide YY / Q000378:metabolism; D012007:Rectum / Q000187:drug effects / Q000378:metabolism*; D013656:Taurocholic Acid / Q000494:pharmacology*; D014479:United Arab Emirates
D001786:Blood Glucose; D002756:Cholagogues and Choleretics; D007328:Insulin; D019894:Peptide YY; D013656:Taurocholic Acid; D052216:Glucagon-Like Peptide 1