Role of Receptors in Expression of Gastrointestinal Hormone Function

Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.

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The Role of Dietary Starches and Sugars and Their Digestive End Products on Gastrointestinal Hormone Release

Dietary Starches and Sugars in Man: A Comparison - ILSI Human Nutrition Reviews ◽

10.1007/978-1-4471-1701-8_6 ◽

1989 ◽

pp. 119-133

Author(s):

T. L. Peeters

Keyword(s):

Gastrointestinal Hormone ◽

Hormone Release ◽

End Products

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Abstract P196: Exacerbation Of Postural Tachycardia Syndrome After An Oral Glucose Challenge: Role Of Incretins

Hypertension ◽

10.1161/hyp.78.suppl_1.p196 ◽

2021 ◽

Vol 78 (Suppl_1) ◽

Author(s):

Nicholas Breier ◽

Andre Diedrich ◽

Luis E Okamoto ◽

Shahram E Mehr ◽

Charles R Flynn ◽

...

Keyword(s):

Peptide Yy ◽

Hormone Secretion ◽

Peripheral Resistance ◽

Postural Tachycardia Syndrome ◽

Oral Glucose ◽

Gastrointestinal Hormone ◽

Postural Tachycardia ◽

Glucose Challenge ◽

Insulinotropic Peptide

Postural Tachycardia Syndrome (POTS) is characterized by excessive upright tachycardia and disabling pre-syncopal symptoms, which are exacerbated after consuming a high-carbohydrate meal. The purpose of this study is to investigate the effect of oral glucose on orthostatic hemodynamic changes and gastrointestinal hormone secretion in POTS. We studied 12 women with POTS and 13 age-matched controls, all subjects received 75-gr oral glucose and 20 mg/kg acetaminophen for nutrient absorption measurement. Hemodynamic, GI hormone secretion and acetaminophen levels were measured at different time-points up to 120-min post-ingestion and while supine and standing. POTS patients had significant upright tachycardia ( delta HR: 48.7 ± 11.2 vs. 23.3 ± 8.1 bpm, P=0.012) and norepinephrine levels (835.2 ± 368.4 vs. 356.9 ± 156.7 pg/mL, P= 0.004). After oral glucose, upright HR significantly increased in POTS (92±15.5 vs. 112± 26 bpm, P=0.002) with a concomitant decline in upright stroke volume (P=0.027); total peripheral resistance, blood pressure and cardiac output remained unaltered. Acetaminophen rate of appearance was similar between groups (P=0.707). POTS patients had increased secretion of C-peptide (P=0.001), Glucose Dependent Insulinotropic Peptide (GIP) (P=0.001), peptide YY (P=0.016) and pancreatic polypeptide (P=0.04), but not GLP-1 (p=0.658) or Glucagon (P=0.836). Only GIP had a time-dependent association with the worsening upright tachycardia and SV fall, figure. Conclusions: Oral glucose exacerbated upright tachycardia in POTS, which was associated with a decline in SV; these changes occurred while GIP, a splanchnic vasodilator, is being maximally secreted.

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Secretin, at the hub of water-salt homeostasis

AJP Renal Physiology ◽

10.1152/ajprenal.00191.2015 ◽

2017 ◽

Vol 312 (5) ◽

pp. F852-F860 ◽

Cited By ~ 1

Author(s):

Jenny Juan Bai ◽

Chong Da Tan ◽

Billy K. C. Chow

Keyword(s):

Central Nervous System ◽

Extracellular Fluid ◽

Receptor Interaction ◽

Gastrointestinal Hormone ◽

Physiological Processes ◽

Osmotic Homeostasis ◽

Water Salt ◽

The Central Nervous System ◽

Salt Homeostasis

Water and salt metabolism are tightly regulated processes. Maintaining this milieu intérieur within narrow limits is critical for normal physiological processes to take place. Disturbances to this balance can result in disease and even death. Some of the better-characterized regulators of water and salt homeostasis include angiotensin II, aldosterone, arginine vasopressin, and oxytocin. Although secretin (SCT) was first described >100 years ago, little is known about the role of this classic gastrointestinal hormone in the maintenance of water-salt homeostasis. In recent years, increasing body of evidence suggested that SCT and its receptor play important roles in the central nervous system and kidney to ensure that the mammalian extracellular fluid osmolarity is kept within a healthy range. In this review, we focus on recent advances in our understanding of the molecular, cellular, and network mechanisms by which SCT and its receptor mediate the control of osmotic homeostasis. Implications of hormonal cross talk and receptor-receptor interaction are highlighted.

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Ubiquitination is involved in glucose-mediated downregulation of GIP receptors in islets

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00070.2007 ◽

2007 ◽

Vol 293 (2) ◽

pp. E538-E547 ◽

Cited By ~ 49

Author(s):

Jie Zhou ◽

Mauren F. A. Livak ◽

Michel Bernier ◽

Denis C. Muller ◽

Olga D. Carlson ◽

...

Keyword(s):

Normal Glucose Tolerance ◽

Diabetic Patients ◽

Intracellular Camp ◽

Gastrointestinal Hormone ◽

Dependent Manner ◽

Type 2 Diabetic Patients ◽

Normal Glucose ◽

Insulinotropic Effect

Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that has a potent stimulatory effect on insulin release under conditions of normal glucose tolerance. However, its insulinotropic effect is reduced or even absent entirely in type 2 diabetic patients. In this study, we addressed the role of glucose concentration in the diabetic range of ≥11 mM, i.e., hyperglycemia per se, as a cause of the lack of response to GIP. Culturing rat and human pancreatic islets in ≥11 mM glucose for up to 24 h resulted in prevention of GIP-mediated intracellular cAMP increase compared with culturing in 5 mM glucose. Western blot analysis revealed a selective 67 ± 2% (rat) and 60 ± 8% (human) decrease of GIP-R expression in islets exposed to ≥11 mM glucose compared with 5 mM glucose ( P < 0.001). We further immunoprecipitated GIP-R from islets and found that GIP-R was targeted for ubiquitination in a glucose- and time-dependent manner. Downregulation of GIP-R was rescued by treating isolated islets with proteasomal inhibitors lactacystin and MG-132, and the islets were once again capable of increasing intracellular cAMP levels in response to GIP. These results suggest that the GIP-R is ubiquitated, resulting in downregulation of the actions of GIP.

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Secretin is not necessary for exocrine pancreatic development and growth in mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00245.2011 ◽

2011 ◽

Vol 301 (5) ◽

pp. G791-G798 ◽

Cited By ~ 6

Author(s):

Maria Dolors Sans ◽

Maria Eugenia Sabbatini ◽

Stephen A. Ernst ◽

Louis G. D'Alecy ◽

Ichiko Nishijima ◽

...

Keyword(s):

Fluid Secretion ◽

Gastrointestinal Hormone ◽

Pancreatic Development ◽

Adaptive Growth ◽

Pancreatic Growth ◽

Secretin Receptor ◽

Camp Levels ◽

Deficient Mice

Adaptive exocrine pancreatic growth is mediated primarily by dietary protein and the gastrointestinal hormone cholecystokinin (CCK). Feeding trypsin inhibitors such as camostat (FOY-305) is known to induce CCK release and stimulate pancreatic growth. However, camostat has also been reported to stimulate secretin release and, because secretin often potentiates the action of CCK, it could participate in the growth response. Our aim was to test the role of secretin in pancreatic development and adaptive growth through the use of C57BL/6 mice with genetic deletion of secretin or secretin receptor. The lack of secretin in the intestine or the secretin receptor in the pancreas was confirmed by RT-PCR. Other related components, such as vasoactive intestinal polypeptide (VIP) receptors (VPAC1and VPAC2), were not affected. Secretin increased cAMP levels in acini from wild-type (WT) mice but had no effect on acini from secretin receptor-deleted mice, whereas VIP and forskolin still induced a normal response. Secretin in vivo failed to induce fluid secretion in receptor-deficient mice. The pancreas of secretin or secretin receptor-deficient mice was of normal size and histology, indicating that secretin is not necessary for normal pancreatic differentiation or maintenance. When WT mice were fed 0.1% camostat in powdered chow, the pancreas doubled in size in 1 wk, accompanied by parallel increases in protein and DNA. Camostat-fed littermate secretin and secretin receptor-deficient mice had similar pancreatic mass to WT mice. These results indicate that secretin is not required for normal pancreatic development or adaptive growth mediated by CCK.

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