Intracolonic Infusion of Bile Salt Stimulates Release of Peptide YY and Inhibits Cholecystokinin-Stimulated Pancreatic Exocrine Secretion in Conscious Dogs

Izukura, Masaaki; Hashimoto, Tsukuru; Gómez, Guillermo A.; Uchida, Tatsuo; Greeley, George H.; Thompson, James C.

doi:10.1097/00006676-199107000-00009

Cited by 19 publications

(13 citation statements)

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“…Exogenous bile salts have been shown to be the most potent stimulus of gut hormones from the endocrine L cells, such as PYY in rabbit colon explants (12), in vivo in conscious dogs (13), and in humans (14). GLP-1, PYY, and bile are released postprandially and in proportion to the amount of calories consumed.…”

Section: Discussionmentioning

confidence: 99%

“…The improved glycemic control in the immediate postoperative period is weight loss independent, because simultaneous improved insulin secretion and reduced insulin resistance have been observed between d 2 and 7 after gastric bypass (9). The early increase in insulin secretion was associated with an enhanced GLP-1 response (9), which may partly be explained by L-cell stimulation from bile acids (12)(13)(14). Moreover, the decrease in insulin resistance may also be the result of increased fasting plasma bile acid levels after gastric bypass surgery (15,16), because firstly, bile acids inhibit gluconeogenesis in an FXR dependent and independent manner (17)(18)(19)(20) and bind to TGR5, leading to cAMP generation and activation of the intracellular type 2 thyroid hormone deiodinase (21).…”

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confidence: 99%

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The Role of Bile After Roux-en-Y Gastric Bypass in Promoting Weight Loss and Improving Glycaemic Control

et al. 2012

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Gastric bypass leads to the remission of type 2 diabetes independently of weight loss. Our hypothesis is that changes in bile flow due to the altered anatomy may partly explain the metabolic outcomes of the operation. We prospectively studied 12 patients undergoing gastric bypass and six patients undergoing gastric banding over a 6-wk period. Plasma fibroblast growth factor (FGF)19, stimulated by bile acid absorption in the terminal ileum, and plasma bile acids were measured. In canine and rodent models, we investigated changes in the gut hormone response after altered bile flow. FGF19 and total plasma bile acids levels increased after gastric bypass compared with no change after gastric banding. In the canine model, both food and bile, on their own, stimulated satiety gut hormone responses. However, when combined, the response was doubled. In rats, drainage of endogenous bile into the terminal ileum was associated with an enhanced satiety gut hormone response, reduced food intake, and lower body weight. In conclusion, after gastric bypass, bile flow is altered, leading to increased plasma bile acids, FGF19, incretin. and satiety gut hormone concentrations. Elucidating the mechanism of action of gastric bypass surgery may lead to novel treatments for type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

The Role of Bile After Roux-en-Y Gastric Bypass in Promoting Weight Loss and Improving Glycaemic Control

et al. 2012

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“…As mentioned earlier, bile acids are able to activate TGR5 (7, 8, 9), resulting in GLP1 secretion from intestinal L cells (12,14). Already in the 1980s, there were reports of bileinduced secretion of GIP (54,55) and glucagon-like reactive materials in dogs (46,57,58,59) and insulin (60). Since then, various groups have reported similar findings (13, 61,62,63,64).…”

Section: Glp1 Secretionmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Bile acid sequestrants in type 2 diabetes: potential effects on GLP1 secretion

Sonne

Hansen

Knop

2014

European Journal of Endocrinology

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Bile acid sequestrants have been used for decades for the treatment of hypercholesterolaemia. Sequestering of bile acids in the intestinal lumen interrupts enterohepatic recirculation of bile acids, which initiate feedback mechanisms on the conversion of cholesterol into bile acids in the liver, thereby lowering cholesterol concentrations in the circulation. In the early 1990s, it was observed that bile acid sequestrants improved glycaemic control in patients with type 2 diabetes. Subsequently, several studies confirmed the finding and recently -despite elusive mechanisms of action -bile acid sequestrants have been approved in the USA for the treatment of type 2 diabetes. Nowadays, bile acids are no longer labelled as simple detergents necessary for lipid digestion and absorption, but are increasingly recognised as metabolic regulators. They are potent hormones, work as signalling molecules on nuclear receptors and G protein-coupled receptors and trigger a myriad of signalling pathways in many target organs. The most described and well-known receptors activated by bile acids are the farnesoid X receptor (nuclear receptor) and the G protein-coupled cell membrane receptor TGR5. Besides controlling bile acid metabolism, these receptors are implicated in lipid, glucose and energy metabolism. Interestingly, activation of TGR5 on enteroendocrine L cells has been suggested to affect secretion of incretin hormones, particularly glucagon-like peptide 1 (GLP1 (GCG)). This review discusses the role of bile acid sequestrants in the treatment of type 2 diabetes, the possible mechanism of action and the role of bile acid-induced secretion of GLP1 via activation of TGR5.

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“…Taurocholic acid (TCA), found in human bile, is a potent TGR5 ligand [7], and in dogs, colonic perfusion with TCA induces PYY secretion [8]. A recent report indicated that TCA enemas could stimulate GLP-1 and PYY secretion in obese patients with type 2 diabetes receiving the dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin [9].…”

Section: Introductionmentioning

confidence: 99%

“…Bile salts bind to the G-protein-coupled TGR5 receptor present on enteroendocrine L-cells [5], with the potential for stimulation of PYY and GLP-1 secretion [6]. Taurocholic acid (TCA), found in human bile, is a potent TGR5 ligand [7], and in dogs, colonic perfusion with TCA induces PYY secretion [8]. A recent report indicated that TCA enemas could stimulate GLP-1 and PYY secretion in obese patients with type 2 diabetes receiving the dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin [9].…”

Section: Introductionmentioning

confidence: 99%

Effects of rectal administration of taurocholic acid on glucagon‐like peptide‐1 and peptide YY secretion in healthy humans

Bound

Standfield

et al. 2012

Diabetes Obesity Metabolism

109

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Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), secreted by enteroendocrine L-cells located most densely in the colon and rectum, are of fundamental importance in blood glucose and appetite regulation. In animal models, colonic administration of bile acids can stimulate GLP-1 and PYY by TGR5 receptor activation. We evaluated the effects of taurocholic acid (TCA), administered as an enema, on plasma GLP-1 and PYY, as well as gastrointestinal sensations in 10 healthy male subjects, and observed that rectal administration of TCA promptly stimulated secretion of both GLP-1 and PYY, and increased fullness, in a dose-dependent manner. These observations confirm that topical application of bile acids to the distal gut may have potential for the management of type 2 diabetes and obesity.

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Intracolonic Infusion of Bile Salt Stimulates Release of Peptide YY and Inhibits Cholecystokinin-Stimulated Pancreatic Exocrine Secretion in Conscious Dogs

Cited by 19 publications

References 0 publications

The Role of Bile After Roux-en-Y Gastric Bypass in Promoting Weight Loss and Improving Glycaemic Control

The Role of Bile After Roux-en-Y Gastric Bypass in Promoting Weight Loss and Improving Glycaemic Control

MECHANISMS IN ENDOCRINOLOGY: Bile acid sequestrants in type 2 diabetes: potential effects on GLP1 secretion

Effects of rectal administration of taurocholic acid on glucagon‐like peptide‐1 and peptide YY secretion in healthy humans

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