2020
DOI: 10.3390/pharmaceutics12090790
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Enteroendocrine Hormone Secretion and Metabolic Control: Importance of the Region of the Gut Stimulation

Abstract: It is now widely appreciated that gastrointestinal function is central to the regulation of metabolic homeostasis. Following meal ingestion, the delivery of nutrients from the stomach into the small intestine (i.e., gastric emptying) is tightly controlled to optimise their subsequent digestion and absorption. The complex interaction of intraluminal nutrients (and other bioactive compounds, such as bile acids) with the small and large intestine induces the release of an array of gastrointestinal hormones from s… Show more

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Cited by 32 publications
(31 citation statements)
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References 223 publications
(275 reference statements)
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“…Along with other mediators, GLP1 is released from EECs in the distal gut. Among nutrient factors (glucose, fat), GLP1 release from EECs is triggered by BA, most likely via stimulation of GPBAR1 (G protein-coupled bile acid receptor 1 also known as TGR5) [17]. Therefore, several therapeutic approaches, including FXR agonists, BA substitution and even bariatric surgery have been evaluated regarding their antidiabetic properties, based on this BA-GLP1 axis [18,19].…”
Section: Discussionmentioning
confidence: 99%
“…Along with other mediators, GLP1 is released from EECs in the distal gut. Among nutrient factors (glucose, fat), GLP1 release from EECs is triggered by BA, most likely via stimulation of GPBAR1 (G protein-coupled bile acid receptor 1 also known as TGR5) [17]. Therefore, several therapeutic approaches, including FXR agonists, BA substitution and even bariatric surgery have been evaluated regarding their antidiabetic properties, based on this BA-GLP1 axis [18,19].…”
Section: Discussionmentioning
confidence: 99%
“…However, the readily absorbed TGR5 agonist SB-756050 failed to stimulate GLP-1 secretion significantly, or improve glycemic control at various doses compared with the placebo in acute studies involving patients with T2D [ 39 ]. It is noteworthy that L-cells are distributed most densely in the distal gut regions [ 13 ]. It would therefore be of interest to investigate whether delivery of TGR5 agonists should be targeted at the distal gut.…”
Section: Effects Of Bile Acids On Gastrointestinal Hormone Secretionmentioning
confidence: 99%
“…For example, the release of ghrelin from gastric G-cells during fasting appears pivotal to sensations of hunger, and stimulation of energy intake. After meals, the secretion of cholecystokinin (CCK) from enteroendocrine I-cells located in the upper gut, and glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) from L-cells located most abundantly in the distal gut, form an integrated signaling system that slows gastrointestinal motility and transit, drives the secretion of insulin to regulate postprandial glucose metabolism (via GLP-1) and suppresses appetite and energy intake [ 13 ]. The role of bile acids in the control of blood glucose and lipid metabolism has been reviewed in detail [ 14 , 15 , 16 , 17 ], but their potential to impact on the regulation of energy intake has received less attention, despite the recognition, since 1968, that oral administration of CDCA and DCA stimulated PYY secretion and suppressed appetite in obese individuals [ 18 ].…”
Section: Introductionmentioning
confidence: 99%
“…GLP‐1 mimetics are now a mainstay in the management of T2DM. [ 155 ] Screening for effective stimuli for GLP‐1 secretion represents an approach to identifying new therapies for T2DM. [ 156 ] To this end, a microfluidic chip system was developed to co‐culture GLUTag cells (GLP‐1 secreting cells) and INS‐1 cells (β cell line) (Figure 11b).…”
Section: The State‐of‐the‐art Sensors For [Ca2+]exmentioning
confidence: 99%