scholarly journals Secretin release after Roux-en-Y Gastric Bypass reveals a population of glucose-sensitive S-cells in distal small intestine

2019 ◽  
Author(s):  
Ida M. Modvig ◽  
Daniel B. Andersen ◽  
Kaare V. Grunddal ◽  
Rune E. Kuhre ◽  
Christoffer Martinussen ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Small Intestine ◽  
Glycemic Control ◽  
Distal Part ◽  
Plasma Concentrations ◽  
Glucose Sensing ◽  
Dependent Manner ◽  
Perfused Rat Pancreas ◽  
Distal Small Intestine ◽  
Somatostatin Secretion

AbstractObjectiveGastrointestinal hormones contribute to the beneficial effects of Roux-en-Y gastric bypass surgery (RYGB) on glycemic control. Secretin is secreted from duodenal S-cells in response to low luminal pH, but it is unknown whether its secretion is altered after RYGB and if secretin contributes to the post-operative improvement in glycemic control. We hypothesized that secretin secretion increases after RYGB as a result of the diversion of nutrients to more distal parts of the small intestine, and thereby affects islet hormone release.MethodsA specific secretin radioimmunoassay was developed, evaluated biochemically, and used to quantify plasma concentrations of secretin in 13 obese individuals before, 1 week after and 3 months after RYGB. Distribution of secretin and its receptor was assessed by RNA-sequencing, mass-spectrometry and in situ hybridization in human and rat tissues. Isolated, perfused rat intestine and pancreas were used to explore the molecular mechanism underlying glucose-induced secretin secretion and to study direct effects of secretin on glucagon, insulin and somatostatin secretion. Secretin was administered alone or in combination with GLP-1 to non-sedated rats to evaluate effects on glucose regulation.ResultsPlasma postprandial secretin was more than doubled in humans after RYGB (P<0.001). The distal small intestine harbored secretin expressing cells in both rats and humans. Glucose increased secretion of secretin in a sodium-glucose co-transporter dependent manner when administered to the distal part but not into the proximal part of the rat small intestine. Secretin stimulated somatostatin secretion (fold change: 1.59, P<0.05) from the perfused rat pancreas but affected neither insulin (P=0.2) nor glucagon (P=0.97) secretion. When administered to rats in vivo, insulin secretion was attenuated and glucagon secretion increased (P=0.04), while blood glucose peak time was delayed (from 15 min to 45 min) and gastric emptying time prolonged (P=0.004).ConclusionGlucose-sensing secretin cells located in the distal part of the small intestine may contribute to increased plasma concentrations observed after RYGB. The metabolic role of the distal S-cells warrants further studies.

scholarly journals Secretin release after Roux-en-Y gastric bypass reveals a population of glucose-sensitive S cells in distal small intestine

2020 ◽  
Vol 44 (9) ◽  
pp. 1859-1871 ◽  
Author(s):  
Ida M. Modvig ◽  
Daniel B. Andersen ◽  
Kaare V. Grunddal ◽  
Rune E. Kuhre ◽  
Christoffer Martinussen ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Small Intestine ◽  
Distal Small Intestine ◽  
Secretin Release

scholarly journals Investigating Intestinal Glucagon After Roux-en-Y Gastric Bypass Surgery

2019 ◽  
Vol 104 (12) ◽  
pp. 6403-6416 ◽  
Author(s):  
Tina Jorsal ◽  
Nicolai J Wewer Albrechtsen ◽  
Marie M Christensen ◽  
Brynjulf Mortensen ◽  
Erik Wandall ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Small Intestine ◽  
Gastric Bypass Surgery ◽  
Plasma Concentrations ◽  
University Hospital ◽  
Morbidly Obese ◽  
Mucosal Biopsy ◽  
Cross Sectional ◽  
Biopsy Specimens ◽  
Before And After

Abstract Context After Roux-en-Y gastric bypass (RYGB) surgery, postprandial plasma glucagon concentrations have been reported to increase. This occurs despite concomitant improved glucose tolerance and increased circulating plasma concentrations of insulin and the glucagon-inhibiting hormone glucagon-like peptide 1 (GLP-1). Objective To investigate whether RYGB-induced hyperglucagonemia may be derived from the gut. Design and Setting Substudy of a prospective cross-sectional study at a university hospital in Copenhagen, Denmark. Participants Morbidly obese individuals undergoing RYGB (n = 8) with or without type 2 diabetes. Interventions Three months before and after RYGB, participants underwent upper enteroscopy with retrieval of gastrointestinal mucosal biopsy specimens. Mixed-meal tests were performed 1 week and 3 months before and after RYGB. Main Outcome Measures The 29–amino acid glucagon concentrations in plasma and in mucosal gastrointestinal biopsy specimens were assessed using mass spectrometry–validated immunoassays, and a new monoclonal antibody reacting with immunoreactive glucagon was used for immunohistochemistry. Results Postprandial plasma concentrations of glucagon after RYGB were increased. Expression of the glucagon gene in the small intestine increased after surgery. Glucagon was identified in the small-intestine biopsy specimens obtained after, but not before, RYGB. Immunohistochemically, mucosal biopsy specimens from the small intestine harbored cells costained for GLP-1 and immunoreactive glucagon. Conclusion Increased concentrations of glucagon were observed in small-intestine biopsy specimens and postprandially in plasma after RYGB. The small intestine harbored cells immunohistochemically costaining for GLP-1 and glucagon-like immunoreactivity after RYGB. Glucagon derived from small-intestine enteroendocrine l cells may contribute to postprandial plasma concentrations of glucagon after RYGB.

scholarly journals Incretin-based therapies: can we achieve glycemic control and cardioprotection?

2013 ◽  
Vol 221 (1) ◽  
pp. T17-T30 ◽  
Author(s):  
Franca S Angeli ◽  
Richard P Shannon
Keyword(s):  
Risk Factors ◽  
Small Intestine ◽  
Insulin Secretion ◽  
Glycemic Control ◽  
Glucagon Secretion ◽  
Peptide Hormone ◽  
Dependent Manner ◽  
Clinical Use ◽  
Dipeptidyl Peptidase 4 ◽  
Preclinical And Clinical Studies

Glucagon-like (GLP-1) is a peptide hormone secreted from the small intestine in response to nutrient ingestion. GLP-1 stimulates insulin secretion in a glucose-dependent manner, inhibits glucagon secretion and gastric emptying, and reduces appetite. Because of the short circulating half-life of the native GLP-1, novel GLP-1 receptor (GLP-1R) agonists and analogs and dipeptidyl peptidase 4 (DPP-4) inhibitors have been developed to facilitate clinical use. Emerging evidence indicates that GLP-1-based therapies are safe and may provide cardiovascular (CV) benefits beyond glycemic control. Preclinical and clinical studies are providing increasing evidence that GLP-1 therapies may positively affect CV function and metabolism by salutary effects on CV risk factors as well as via direct cardioprotective actions. However, the mechanisms whereby the various classes of incretin-based therapies exert CV effects may be mechanistically distinct and may not necessarily lead to similar CV outcomes. In this review, we will discuss the potential mechanisms and current understanding of CV benefits of native GLP-1, GLP-1R agonists and analogs, and of DPP-4 inhibitor therapies as a means to compare their putative CV benefits.

scholarly journals Lipoprotein Subclass Profile after Progressive Energy Deficits Induced by Calorie Restriction or Exercise

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1814 ◽  
Author(s):  
Yu Chooi ◽  
Cherlyn Ding ◽  
Zhiling Chan ◽  
Jezebel Lo ◽  
John Choo ◽  
...  
Keyword(s):  
Energy Balance ◽  
Aerobic Exercise ◽  
Calorie Restriction ◽  
Plasma Concentrations ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
Energy Deficit ◽  
Dependent Manner ◽  
Blood Lipid Profile ◽  
Diet And Exercise

Weight loss, induced by chronic energy deficit, improves the blood lipid profile. However, the effects of an acute negative energy balance and the comparative efficacy of diet and exercise are not well-established. We determined the effects of progressive, acute energy deficits (20% or 40% of daily energy requirements) induced by a single day of calorie restriction (n = 19) or aerobic exercise (n = 13) in healthy subjects (age: 26 ± 9 years; body mass index (BMI): 21.8 ± 2.9 kg/m2). Fasting plasma concentrations of very low-, intermediate-, low-, and high-density lipoprotein (VLDL, LDL, IDL, and HDL, respectively) particles and their subclasses were determined using nuclear magnetic resonance. Total plasma triglyceride and VLDL-triglyceride concentrations decreased after calorie restriction and exercise (all p ≤ 0.025); the pattern of change was linear with an increasing energy deficit (all p < 0.03), with no evidence of plateauing. The number of circulating large and medium VLDL particles decreased after diet and exercise (all p < 0.015), with no change in small VLDL particles. The concentrations of IDL, LDL, and HDL particles, their relative distributions, and the particle sizes were not altered. Our data indicate that an acute negative energy balance induced by calorie restriction and aerobic exercise reduces triglyceride concentrations in a dose-dependent manner, by decreasing circulating large and medium VLDL particles.

scholarly journals The Effect of an Encapsulated Nutrient Mixture on Food Intake and Satiety: A Double-Blind Randomized Cross-Over Proof of Concept Study

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1787 ◽  
Author(s):  
Annick Alleleyn ◽  
Mark van Avesaat ◽  
Dina Ripken ◽  
Sinéad Bleiel ◽  
Daniel Keszthelyi ◽  
...  
Keyword(s):  
Small Intestine ◽  
Food Intake ◽  
Area Under The Curve ◽  
Double Blind ◽  
Distal Small Intestine ◽  
Active Product ◽  
Non Invasive ◽  
Control Product ◽  
Scale Scores ◽  
And Control

Activation of the intestinal brake by infusing nutrients into the distal small intestine with catheters inhibits food intake and enhances satiety. Encapsulation of macronutrients, which protects against digestion in the proximal gastrointestinal tract, can be a non-invasive alternative to activate this brake. In this study, we investigate the effect of oral ingestion of an encapsulated casein and sucrose mixture (active) targeting the distal small intestine versus a control product designed to be released in the stomach on food intake, satiety, and plasma glucose concentrations. Fifty-nine volunteers received the active and control product on two separate test days. Food intake was determined during an ad libitum meal 90 min after ingestion of the test product. Visual analogue scale scores for satiety and blood samples for glucose analysis were collected at regular intervals. Ingestion of the active product decreased food intake compared to the control product (655 kcal compared with 699 kcal, respectively, p < 0.05). The area under the curve (AUC) for hunger was decreased (p < 0.05) and AUC for satiety was increased (p < 0.01) after ingestion of the active product compared to the control product. Ingestion of an encapsulated protein-carbohydrate mixture resulted in inhibition of food intake compared to a non-encapsulated control product.

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