The bile acid‐sequestering resin sevelamer eliminates the acute <scp>GLP</scp>‐1 stimulatory effect of endogenously released bile acids in patients with type 2 diabetes

Brønden, Andreas; Albèr, Anders; Rohde, Ulrich; Gasbjerg, Lærke S.; Rehfeld, Jens F.; Holst, Jens J.; Vilsbøll, Tina; Knop, Filip K.

doi:10.1111/dom.13080

Cited by 37 publications

(26 citation statements)

References 42 publications

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“…96 Bile salts stimulate Takeda G-protein-coupled receptor-5 (TGR5) on the basolateral aspect of the enteric endocrine L cells to elicit GLP-1 secretion. 97 CCK activation of NTS-CC-i neurons may also inhibit DMV-C-e via the α2-adrenergic receptors. All these actions of CCK lead to robust gastric inhibition and slowed gastric emptying.…”

Section: G a S Tric " B R Aking" Hormone Smentioning

confidence: 99%

“…It has been reported that entry of chyme in the gut releases nesfatin‐1 that stimulates CCK secretion that causes gallbladder emptying and rise in bile salts . Bile salts stimulate Takeda G‐protein‐coupled receptor‐5 (TGR5) on the basolateral aspect of the enteric endocrine L cells to elicit GLP‐1 secretion . CCK activation of NTS‐CC‐i neurons may also inhibit DMV‐C‐e via the α2‐adrenergic receptors.…”

Section: Gastric “Braking” Hormonesmentioning

confidence: 99%

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Advances in the physiology of gastric emptying

Goyal

Guo

Mashimo

2019

Neurogastroenterology Motil

224

154

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There have been many recent advances in the understanding of various aspects of the physiology of gastric motility and gastric emptying. Earlier studies had discovered the remarkable ability of the stomach to regulate the timing and rate of emptying of ingested food constituents and the underlying motor activity. Recent studies have shown that two parallel neural circuits, the gastric inhibitory vagal motor circuit (GIVMC) and the gastric excitatory vagal motor circuit (GEVMC), mediate gastric inhibition and excitation and therefore the rate of gastric emptying. The GIVMC includes preganglionic cholinergic neurons in the DMV and the postganglionic inhibitory neurons in the myenteric plexus that act by releasing nitric oxide, ATP, and peptide VIP. The GEVMC includes distinct gastric excitatory preganglionic cholinergic neurons in the DMV and postganglionic excitatory cholinergic neurons in the myenteric plexus. Smooth muscle is the final target of these circuits. The role of the intramuscular interstitial cells of Cajal in neuromuscular transmission remains debatable. The two motor circuits are differentially regulated by different sets of neurons in the NTS and vagal afferents. In the digestive period, many hormones including cholecystokinin and GLP‐1 inhibit gastric emptying via the GIVMC, and in the inter‐digestive period, hormones ghrelin and motilin hasten gastric emptying by stimulating the GEVMC. The GIVMC and GEVMC are also connected to anorexigenic and orexigenic neural pathways, respectively. Identification of the control circuits of gastric emptying may provide better delineation of the pathophysiology of abnormal gastric emptying and its relationship to satiety signals and food intake.

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Section: G a S Tric " B R Aking" Hormone Smentioning

confidence: 99%

Section: Gastric “Braking” Hormonesmentioning

confidence: 99%

Advances in the physiology of gastric emptying

Goyal

Guo

Mashimo

2019

Neurogastroenterology Motil

224

154

View full text Add to dashboard Cite

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“…Bile acid sequestrants, which inhibit bile acid resorption, thereby increasing the amount of bile in the distal gut, have been investigated as a therapy for T2DM . While reducing blood glucose modestly, bile acid sequestrants have been reported to decrease GLP‐1 secretion when combined with either exogenous bile, in both people with and without T2DM, or endogenous bile (released from the gallbladder in response to intravenous infusion of cholecystokinin) in T2DM . The reduction of GLP‐1 would intuitively worsen glucose control.…”

Section: Gastrointestinal Effects Of Metformin: Role Of Gut Peptidesmentioning

confidence: 99%

“…70 While reducing blood glucose modestly, bile acid sequestrants have been reported to decrease GLP-1 secretion when combined with either exogenous bile, in both people with and without T2DM, 50 or endogenous bile (released from the gallbladder in response to intravenous infusion of cholecystokinin) in T2DM. 71 The reduction of GLP-1 would intuitively worsen glucose control. Therefore, GLP-1 secretion does not appear to account for the benefits of bile acid sequestrants.…”

Section: Bile Acids and Glp-1mentioning

confidence: 99%

Mechanism of glucose‐lowering by metformin in type 2 diabetes: Role of bile acids

Sansome

Xie

Veedfald

et al. 2019

Diabetes Obesity Metabolism

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Type 2 diabetes mellitus (T2DM) is an increasingly prevalent chronic condition, characterized by abnormally elevated blood glucose concentrations and, as a consequence, increased risk of micro‐ and macrovascular complications. Metformin is usually the first‐line glucose‐lowering medication in T2DM; however, despite being used for more than 60 years, the mechanism underlying the glucose‐lowering action of metformin remains incompletely understood. Although metformin reduces hepatic glucose production, there is persuasive evidence that the gastrointestinal tract is crucial in mediating this effect, particularly via secretion of the incretin hormone glucagon‐like peptide 1 (GLP‐1). It is now well recognized that bile acids, in addition to their established function in fat digestion and absorption, are important regulators of glucose metabolism. Exposure of the small and large intestine to bile acids induces GLP‐1 secretion, modulates the composition of the gut microbiota, and reduces postprandial blood glucose excursions in humans with and without T2DM. Metformin reduces intestinal bile acid resorption substantially, such that intraluminal bile acids may, at least in part, account for its glucose‐lowering effect. The present review focuses on the conceptual shift in our understanding as to how metformin lowers blood glucose in T2DM, with a particular emphasis on the role of intestinal bile acids.

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“…TGR5 activity appears to not have been lost in type 2 diabetic humans whereby the infusion of CCK, or rectal taurocholate, causes GLP-1 and insulin release via the TGR5 axis in colonic L-cells and pancreatic β-cells respectively ( 341 , 342 ).…”

Section: Tgr5mentioning

confidence: 99%

Dissecting the Physiology and Pathophysiology of Glucagon-Like Peptide-1

Paternoster

Falasca

2018

Front. Endocrinol.

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An aging world population exposed to a sedentary life style is currently plagued by chronic metabolic diseases, such as type-2 diabetes, that are spreading worldwide at an unprecedented rate. One of the most promising pharmacological approaches for the management of type 2 diabetes takes advantage of the peptide hormone glucagon-like peptide-1 (GLP-1) under the form of protease resistant mimetics, and DPP-IV inhibitors. Despite the improved quality of life, long-term treatments with these new classes of drugs are riddled with serious and life-threatening side-effects, with no overall cure of the disease. New evidence is shedding more light over the complex physiology of GLP-1 in health and metabolic diseases. Herein, we discuss the most recent advancements in the biology of gut receptors known to induce the secretion of GLP-1, to bridge the multiple gaps into our understanding of its physiology and pathology.

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The bile acid‐sequestering resin sevelamer eliminates the acute GLP‐1 stimulatory effect of endogenously released bile acids in patients with type 2 diabetes

Abstract: Single-dose administration of sevelamer eliminated bile acid-mediated GLP-1 secretion in patients with type 2 diabetes, which could be explained by reduced bile acid stimulation of the basolaterally localized TGR5 on enteroendocrine L cells.

Cited by 37 publications

References 42 publications

Advances in the physiology of gastric emptying

Advances in the physiology of gastric emptying

Mechanism of glucose‐lowering by metformin in type 2 diabetes: Role of bile acids

Dissecting the Physiology and Pathophysiology of Glucagon-Like Peptide-1

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