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

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.

Download Full-text

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

Nutrients ◽

10.3390/nu10111787 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1787 ◽

Cited By ~ 5

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.

Download Full-text

Sequence, tissue distribution, and functional characterization of the rat fructose transporter GLUT5

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1993.264.6.g1169 ◽

1993 ◽

Vol 264 (6) ◽

pp. G1169-G1176 ◽

Cited By ~ 18

Author(s):

E. B. Rand ◽

A. M. Depaoli ◽

N. O. Davidson ◽

G. I. Bell ◽

C. F. Burant

Keyword(s):

Small Intestine ◽

Functional Characterization ◽

Cdna Probe ◽

Amino Acid Identity ◽

Human Testis ◽

Cdna Clones ◽

Rat Tissues ◽

Rat Small Intestine ◽

Cross Hybridization ◽

Distal Small Intestine

cDNA clones encoding rat GLUT5-small intestinal facilitative hexose transporter were isolated from a jejunum library by cross-hybridization with a human GLUT5 cDNA probe. The cDNA sequence indicates that rat GLUT5 is composed of 502 amino acids and has 81.5% amino acid identity and 87.3% similarity with the sequence of human GLUT5. Expression of synthetic rat GLUT5 mRNA in Xenopus oocytes showed that rat GLUT5 was able to mediate the uptake of fructose and, to a lesser extent, of glucose. RNA blotting studies showed that GLUT5 mRNA was present in rat small intestine, kidney, and brain. Although GLUT5 mRNA is expressed in human testis, adipose tissue, and skeletal muscle, it could not be detected by RNA blotting in these rat tissues. Developmental studies showed low levels of GLUT5 mRNA in rat small intestine and kidney during the prenatal period with a rapid induction of GLUT5 expression occurring postnatally. In situ hybridization studies of GLUT5 mRNA expression in the small intestine revealed differential expression along the crypt-villus axis with the highest levels of mRNA being in the midvillus region. In addition, there was quantitatively more GLUT5 mRNA detected in the proximal as opposed to the distal small intestine.

Download Full-text

Gastrointestinal motor effects of erythromycin

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1990.259.3.g355 ◽

1990 ◽

Vol 259 (3) ◽

pp. G355-G363 ◽

Cited By ~ 6

Author(s):

M. F. Otterson ◽

S. K. Sarna

Keyword(s):

Small Intestine ◽

Cycle Length ◽

Amplitude Ratio ◽

Contractile Activity ◽

Low Doses ◽

Control Activity ◽

Distal Small Intestine ◽

Gastrointestinal Motor ◽

High Doses ◽

Motor Effects

We studied the small intestinal motor effects of oral and intravenous (iv) erythromycin in 10 conscious dogs. After control recordings with placebo, oral or iv erythromycin was given at 40% of the migrating motor complex (MMC) cycle. Recordings were made after administration until normal contractile activity had returned or 12 h postdrug administration. Low doses initiated a premature MMC. High doses, however, prolonged the MMC cycle length. Erythromycin reduced the MMC propagation velocity at all doses. Both oral and iv erythromycin induced amyogenesia. During this pattern, electrical control activity was obliterated in the proximal and destabilized in the distal small intestine. Erythromycin also increased the incidence of retrograde giant contractions (RGCs) and vomiting. These effects occurred within the first 2 h after oral and within the first 30 min after iv administration. The incidence of giant migrating contractions (GMCs) increased significantly from 5 to 12 h but not from 0 to 5 h after administration. The distance of origination of GMCs from the ileocolonic junction was significantly increased from 5 to 12 h. The amplitude ratio, duration, and velocity of migration of GMCs induced after erythromycin were similar to control values. Clusters of coordinated antral and duodenal contractions also occurred early after administration. Our findings suggest that erythromycin has multiple motor effects on the stomach and small intestine. Diarrhea, abdominal cramping, and vomiting associated with erythromycin may be related to increased incidence of GMCs and RGCs. Erythromycin has a biphasic effect on MMC cycle length, initiating premature MMCs at low doses and prolonging their cycle length at higher doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text

Oxidation of glucose carbon entering the TCA cycle is reduced by glutamine in small intestine epithelial cells

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1995.268.6.g879 ◽

1995 ◽

Vol 268 (6) ◽

pp. G879-G888 ◽

Cited By ~ 4

Author(s):

C. E. Kight ◽

S. E. Fleming

Keyword(s):

Small Intestine ◽

Epithelial Cells ◽

Glucose Oxidation ◽

Tca Cycle ◽

Proximal Segment ◽

Distal Small Intestine ◽

Glucose Carbon ◽

The Tca Cycle ◽

Oxidation Of Glucose ◽

In Cells

The influence of glutamine on glucose oxidation was assessed in epithelial cells isolated from the mucosa of the proximal, mid-, and distal small intestine of young, fed, male rats. Glucose oxidation declined along the length of the small intestine, with values from the mid- and distal segments representing approximately 55% and 40%, respectively, of the value from the proximal segment. A gradient along the small intestine was noted also in the influence of glutamine on glucose oxidation: glutamine suppressed glucose oxidation approximately 60% in the proximal small intestine, 39% in the mid-intestine, and 31% in the distal small intestine. Glutamine suppressed the oxidation of glucose carbon that entered the tricarboxylic acid (TCA) cycle; this was determined using CO2 ratios derived from acetate and glucose isotopes. In cells from the proximal segment, the probability that carbon entering the cycle would complete one full turn was reduced by glutamine from 0.77 to 0.28. The entry of glucose-derived pyruvate into the TCA cycle did not appear to be influenced by the presence of glutamine, however. Glutamine had no influence on the proportion of glucose metabolism that occurred via the pentose phosphate pathway (which averaged 5% or less), but reduced flux of carbon through pyruvate carboxylase relative to flux through pyruvate dehydrogenase from 40% to 9% in cells from the proximal segment. These data suggest that, in the presence of glutamine, the fate of pyruvate carbon (derived from glucose or elsewhere) entering the TCA cycle is altered from that of oxidation to anaplerosis and subsequent efflux of TCA cycle intermediates into newly synthesized compounds.

Download Full-text

Sodium, potassium, and intestinal transport of glucose, l-tyrosine, phosphate, and calcium

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1963.205.1.107 ◽

1963 ◽

Vol 205 (1) ◽

pp. 107-111 ◽

Cited By ~ 51

Author(s):

Harold E. Harrison ◽

Helen C. Harrison

Keyword(s):

Small Intestine ◽

Calcium Transport ◽

Inorganic Phosphate ◽

Choline Chloride ◽

Sodium Concentration ◽

Phosphate Transport ◽

Metabolic Energy ◽

Transport Systems ◽

Bicarbonate Buffer ◽

Distal Small Intestine

Everted loops of rat small intestine were incubated in media varying in their concentrations of sodium and potassium. Reduction of sodium concentration was effected by substitution of choline chloride in equimolar amounts for sodium chloride in the saline-bicarbonate buffer. Concentrative transport of glucose, l-tyrosine, inorganic phosphate, and calcium was measured by determination of the final ratio of the concentrations of the solute in serosal and mucosal fluids, and the increment of the solute in serosal fluid during incubation. Ca45 was used as an indicator of calcium distribution. The glucose, l-tyrosine, and inorganic phosphate transport systems require sodium, and at a submaximal concentration of sodium an increased concentration of potassium is inhibitory. The calcium transport system does not require sodium and in loops from the distal small intestine calcium transport is enhanced by reduction of sodium concentration in the medium. It is postulated that there is a common sodium-requiring system which is necessary for the linkage of metabolic energy to glucose, amino acid, and inorganic phosphate transport.

Download Full-text

Glucose and glutamine provide similar proportions of energy to mucosal cells of rat small intestine

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1997.273.4.g968 ◽

1997 ◽

Vol 273 (4) ◽

pp. G968-G978 ◽

Cited By ~ 20

Author(s):

Sharon E. Fleming ◽

Kirsten L. Zambell ◽

Mark D. Fitch

Keyword(s):

Small Intestine ◽

Epithelial Cells ◽

Metabolic Pathways ◽

Glycolytic Flux ◽

Net Energy ◽

Intestinal Epithelial ◽

Atp Production ◽

Distal Small Intestine ◽

Mucosal Cells ◽

In Cells

The objectives of this study were to establish a reliable method for quantifying glycolytic flux in intestinal epithelial cells, to determine the proportion of energy provided to small intestine epithelial cells by glucose vs. glutamine, and to determine whether there was an energetic advantage to having both substrates present simultaneously. There was substantial retention of 3H in alanine and lactate when [2-3H]glucose was used as tracer for quantifying glycolysis, and the magnitude of the3H retention was influenced by the presence of other substrates and metabolites. Detritiation was at least 99% complete, however, when [3-3H]glucose was used as tracer in this system and the tritium was recovered as3H2O. Glycolytic flux was six- to sevenfold higher in cells of the proximal than distal small intestine but was not significantly different for young adult (4 mo) vs. aged adult (24 mo) rats. Net ATP production from exogenous substrates was higher when both glucose and glutamine were present simultaneously than when either substrate was present alone, and glucose was calculated to provide 50–60% of the net ATP produced from these two substrates. Most of the energy produced from glucose was produced via the anaerobic metabolic pathways (78% for glucose alone, 95% with glucose and glutamine). Net energy production was calculated to be 10% lower in cells from aged animals than in those from young animals, since CO2 production from these major substrates was lower in cells from aged animals.

Download Full-text

The Effect of Standard versus Longer Intestinal Bypass on GLP-1 Regulation and Glucose Metabolism in Patients with Type 2 Diabetes Undergoing Roux-en-Y Gastric Bypass. The Long-Limb study

10.2337/figshare.12814262.v1 ◽

2020 ◽

Author(s):

Alexander Dimitri Miras ◽

Anna Kamocka ◽

Belén Pérez-Pevida ◽

Sanjay Purkayastha ◽

Krishna Moorthy ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gastric Bypass ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Mechanistic Study ◽

Intestinal Bypass ◽

Distal Small Intestine ◽

Time To Peak ◽

Biliopancreatic Limb

Objective Roux-en-Y gastric bypass (RYGB) characteristically enhances post-prandial levels of Glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesised that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the post-prandial peak in GLP-1, translating into higher insulin secretion and thus additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass. Research Design and Methods Fifty-three patients with type 2 diabetes and obesity were randomised to either ‘standard limb’ RYGB (50cm biliopancreatic limb) or ‘long limb’ RYGB (150cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycaemic hyperinsulinaemic clamps at baseline, 2 weeks and at 20% weight loss after surgery. Results Both groups exhibited enhancement in post-prandial GLP-1 secretion and improvements in glycaemia compared to baseline. There were no significant differences in post-prandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity. Conclusion The findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.

Download Full-text

Diagnosis of the Syndrome of Excessive Bacterial Growth of the Small Intestine in Patients with Bauhinia Insufficiency and After its Surgical Correction (First Results)

10.47363/jpr/2020(2)116 ◽

2020 ◽

pp. 1-6

Author(s):

Vladimir Leonidovich Martynov ◽

◽

Natalia Vladimirovna Kazarina ◽

Keyword(s):

Small Intestine ◽

Bacterial Growth ◽

Ileocecal Valve ◽

Normal Function ◽

Main Group ◽

Surgical Correction ◽

Control Group ◽

Distal Small Intestine ◽

First Results ◽

Respiratory Test

Objective: To determine the syndrome of excessive bacterial growth in the small intestine (SIBO) in patients with insufficiency of the bauhinia valve (NBZ) and after its surgical correction. Methods of examination: Patients of the studied groups were examined using direct and indirect methods of diagnosis of SIBO. Bacteriological examination of ileal aspirate and other surgical material was performed. All patients underwent a hydrogen respiratory test with a load of lactulose and performed a qualitative reaction of urine to indican. Characteristics of the material: 50 patients were examined, of which 30 were included in the main group, who underwent surgical correction of NBZ - Bauginoplasty; 20 patients are included in the control group in which the ileocecal valve is consistent. Patients of the main group were examined before surgery and on the 7th and 45th day after Bauhinoplasty. Main results: All patients of the main group had SIBS of varying severity, in 80% of patients SIBS was localized in the distal small intestine. Patients with normal function of ileocecal valve syndrome of excessive bacterial growth did not suffer. Intraoperatively, 76% of patients showed signs of mesenteric mesentery of the small intestine, and the fact of bacterial translocation in SIBO was also confirmed. After 7 days after surgical correction of the Bauhinia valve, the normalization of peak and background excretion of hydrogen was observed in 37% of patients. For 45 days in all patients the hydrogen curve corresponded to the norm. Conclusions: the deficiency of the bauhinia valve is obligately accompanied by the syndrome of excessive bacterial growth in the small intestine, surgical correction is an effective method for correcting the syndrome of excessive bacterial growth in patients with NBD.

Download Full-text

Inhibitory role of the distal small intestine on the gastric secretory response to meals in man

Gastroenterology ◽

10.1016/0016-5085(78)90247-0 ◽

1978 ◽

Vol 74 (4) ◽

pp. 704-707 ◽

Cited By ~ 27

Author(s):

Jonathan E. Clain ◽

Vay Liang W. Go ◽

Juan-R. Malagelada

Keyword(s):

Small Intestine ◽

Secretory Response ◽

Distal Small Intestine ◽

Inhibitory Role

Download Full-text