Andreas Brønden A, et al. – The objective of this research was to evaluate the glucagon–like peptide–1 (GLP–1)secretory and gluco–metabolic impacts of endogenously released bile, with and without concomitant administration of the bile acid–sequestering resin, sevelamer, in patients with type 2 diabetes. It was showed that single–dose administration of sevelamer eliminated bile acid–mediated glucagon–like peptide–1 (GLP–1) secretion in patients with type 2 diabetes, which could be explained by reduced bile acid stimulation of the basolaterally localized takeda G protein–coupled receptor 5 (TGR5) on enteroendocrine L cells.

Methods

• Researchers conducted a randomized, placebo-controlled, and double-blinded cross-over study including 15 metformin-treated patients with type 2 diabetes.
• Thereafter, 4 experimental study days in randomized order with administration of either sevelamer 3,200 mg or placebo in combination with intravenous infusion of cholecystokinin (CCK) (0.4 pmol sulfated CCK-8/kg/min).
• The preliminary outcome was plasma GLP-1 excursions as measured by incremental area under the curve.
• Plasma responses of glucose, triglycerides, insulin, CCK, fibroblast growth factor-19 and 7α-hydroxy-4-cholesten-3-one (C4) were considered as secondary outcomes.
• They evaluated gallbladder dynamics, gastric emptying, resting energy expenditure, appetite and ad libitum food intake.

Results

• Compared to saline, CCK-mediated gallbladder emptying was demonstrated to elicit a significant induction of GLP-1 secretion, whereas concomitant single-dose administration of the bile acid sequestrant sevelamer was shown to eliminate the acute bile acid-induced increase in plasma GLP-1 excursions.