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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Rectal taurocholate increases L cell and insulin secretion, and decreases blood glucose and food intake in obese type 2 diabetic volunteers
Diabetologia, Volume 55, No. 9, Year 2012
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Description
Aims/hypothesis: 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 ED50 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/interpretation: Therapies that increase bile salts (or their mimics) in the distal bowel may be valuable in the treatment of type 2 diabetes and obesity. © 2012 Springer-Verlag.
Authors & Co-Authors
Adrian, Thomas E.
United Arab Emirates, Al Ain
United Arab Emirates University
Gariballa, Salah E.
United Arab Emirates, Al Ain
United Arab Emirates University
Parekh, Khatija A.
United Arab Emirates, Al Ain
United Arab Emirates University
Thomas, Sneha Ann
United Arab Emirates, Al Ain
United Arab Emirates University
Saadi, Hussein F.
United Arab Emirates, Al Ain
United Arab Emirates University
Al-Kaabi, Juma M.
United Arab Emirates, Al Ain
United Arab Emirates University
Nagelkerke, Nico J.D.
United Arab Emirates, Al Ain
United Arab Emirates University
Gedulin, Bronislava R.
United States, San Diego
Satiogen Pharmaceuticals
Young, Andrew A.
United States, Philadelphia
Glaxosmithkline, Usa
Statistics
Citations: 125
Authors: 9
Affiliations: 3
Identifiers
Doi:
10.1007/s00125-012-2593-2
ISSN:
0012186X
e-ISSN:
14320428
Research Areas
Disability
Food Security
Health System And Policy
Noncommunicable Diseases