Concurrent duodenal manometric and impedance recording to evaluate the effects of hyoscine on motility and flow events, glucose absorption, and incretin release

2007 ◽  
Vol 292 (4) ◽  
pp. G1099-G1104 ◽  
Author(s):  
Reawika Chaikomin ◽  
Keng Liang Wu ◽  
Selena Doran ◽  
Karen L. Jones ◽  
Andre J. P. M. Smout ◽  
...  

Upper gastrointestinal motor function and incretin hormone secretion are major determinants of postprandial glycemia and insulinemia. However, the impact of small intestinal flow events on glucose absorption and incretin release is poorly defined. Intraluminal impedance monitoring is a novel technique that allows flow events to be quantified. Eight healthy volunteers were studied twice, in random order. A catheter incorporating six pairs of electrodes at 3-cm intervals, and six corresponding manometry sideholes, was positioned in the duodenum. Hyoscine butylbromide (20 mg) or saline was given as an intravenous bolus, followed by a continuous intravenous infusion of either hyoscine (20 mg/h) or saline over 60 min. Concurrently, glucose and 3- O-methylglucose (3-OMG) were infused into the proximal duodenum (3 kcal/min), with frequent blood sampling to measure glucose, 3-OMG, insulin, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The frequency of duodenal pressure waves and propagated pressure wave sequences was reduced by hyoscine in the first 10 min ( P < 0.01 for both), but not after that time. In contrast, there were markedly fewer duodenal flow events throughout 60 min with hyoscine ( P < 0.005). Overall, blood glucose ( P < 0.01) and plasma 3-OMG concentrations ( P < 0.05) were lower during hyoscine than saline, whereas plasma insulin, GLP-1, and GIP concentrations were initially ( t = 20 min) lower during hyoscine ( P < 0.05). In conclusion, intraluminal impedance measurement may be more sensitive than manometry in demonstrating alterations in duodenal motor function. A reduction in the frequency of duodenal flow events is associated with a decreased rate of glucose absorption and incretin release in healthy subjects.

2010 ◽  
Vol 299 (6) ◽  
pp. G1326-G1333 ◽  
Author(s):  
Paul Kuo ◽  
Max Bellon ◽  
Judith Wishart ◽  
André J. Smout ◽  
Richard H. Holloway ◽  
...  

The contribution of small intestinal motor activity to nutrient absorption is poorly defined. A reduction in duodenal flow events after hyoscine butylbromide, despite no change in pressure waves, was associated with reduced secretion of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) and a delay in glucose absorption. The aim of this study was to investigate the effect of metoclopramide on duodenal motility and flow events, incretin hormone secretion, and glucose absorption. Eight healthy volunteers (7 males and 1 female; age 29.8 ± 4.6 yr; body mass index 24.5 ± 0.9 kg/m2) were studied two times in randomized order. A combined manometry and impedance catheter was used to measure pressure waves and flow events in the same region of the duodenum simultaneously. Metoclopramide (10 mg) or control was administered intravenously as a bolus, followed by an intraduodenal glucose infusion for 60 min (3 kcal/min) incorporating the14C-labeled glucose analog 3- O-methylglucose (3-OMG). We found that metoclopramide was associated with more duodenal pressure waves and propagated pressure sequences than control ( P < 0.05 for both) during intraduodenal glucose infusion. However, the number of duodenal flow events, blood glucose concentration, and plasma 3-[14C]OMG activity did not differ between the two study days. Metoclopramide was associated with increased plasma concentrations of GLP-1 ( P < 0.05) and GIP ( P = 0.07) but lower plasma insulin concentrations ( P < 0.05). We concluded that metoclopramide was associated with increased frequency of duodenal pressure waves but no change in duodenal flow events and glucose absorption. Furthermore, GLP-1 and GIP release increased with metoclopramide, but insulin release paradoxically decreased.


Author(s):  
Tejaswini Arunachala Murthy ◽  
Jacqueline Grivell ◽  
Seva Hatzinikolas ◽  
Lee-anne S Chapple ◽  
Marianne J Chapman ◽  
...  

Abstract Context Hypoglycemia is a major barrier to optimal glycemic control in insulin-treated diabetes. Recent guidelines from the American Diabetes Association have subcategorized “non-severe” hypoglycemia into level 1 (&lt;3.9 mmol/L) and 2 (&lt;3 mmol/L) hypoglycemia. Gastric emptying of carbohydrate is a major determinant of postprandial glycemia but its role in hypoglycemia counter-regulation remains underappreciated. “Marked” hypoglycemia (~2.6 mmol/L) accelerates gastric emptying and increases carbohydrate absorption in health and type 1 diabetes, but the impact of “mild” hypoglycemia (3.0-3.9 mmol/L) is unknown. Objective To determine the effects of 2 levels of hypoglycemia, 2.6 mmol/L (“marked”) and 3.6 mmol/L (“mild”), on gastric emptying in health. Design, Setting, and Subjects Fourteen healthy male participants (mean age: 32.9 ± 8.3 years; body mass index: 24.5 ± 3.4 kg/m2) from the general community underwent measurement of gastric emptying of a radiolabeled solid meal (100 g beef) by scintigraphy over 120 minutes on 3 separate occasions, while blood glucose was maintained at either ~2.6 mmol/L, ~3.6 mmol/L, or ~6 mmol/L in random order from 15 minutes before until 60 minutes after meal ingestion using glucose-insulin clamp. Blood glucose was then maintained at 6 mmol/L from 60 to 120 minutes on all days. Results Gastric emptying was accelerated during both mild (P = 0.011) and marked (P = 0.001) hypoglycemia when compared to euglycemia, and was more rapid during marked compared with mild hypoglycemia (P = 0.008). Hypoglycemia-induced gastric emptying acceleration during mild (r = 0.57, P = 0.030) and marked (r = 0.76, P = 0.0014) hypoglycemia was related to gastric emptying during euglycemia. Conclusion In health, acceleration of gastric emptying by insulin-induced hypoglycemia is dependent on the degree of hypoglycemia and baseline rate of emptying.


Author(s):  
Simon Veedfald ◽  
Jens Frederik Rehfeld ◽  
Gerrit van Hall ◽  
Lars Bo Svendsen ◽  
Jens Juul Holst

Abstract Context Entero-pancreatic hormone secretion has been reported during the pre-absorptive cephalic and gastric meal phases, but never with a blood sampling frequency providing a temporal resolution that allows close scrutiny and correlations with gastric emptying and glucose-absorption. Objective We hypothesized that entero-pancreatic hormone secretion after nutrient ingestion would be rapid and correlate with gastric emptying and glucose absorption. Design and setting Two visits in a clinical research facility. Participants Ten healthy young men. Interventions A 75g glucose drink (OG) and a liquid mixed meal (LMM) were ingested (t 0-2 min) on separate days. Acetaminophen and 3-O-methyl-D-glucopyranose (3-OMG) were added to the drinks to evaluate gastric emptying and glucose absorption, respectively. Arterialized venous blood was sampled (t -30,-20,-18,-16,-14,-12,-10,-8,-6,-4,-2, 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 30 min). Main outcome measures Plasma glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), gastrin, cholecystokinin (CCK), glucagon, pancreatic polypeptide (PP), 3-OMG and glucose. Serum insulin, C-peptide and acetaminophen. Results Acetaminophen increased 8min after OG(p&lt;0.001) and LMM(p&lt;0.05). 3-OMG; 8min after LMM(p&lt;0.0001), 10min after OG(p=0.04). PP; 4min after LMM(p&lt;0.03). Gastrin; 6min after LMM(p&lt;0.003) and OG(p&lt;0.003). CCK; 6min after LMM(p=0.0001). GIP; 8min after OG(p&lt;0.05) and LMM(p&lt;0.03). Glucose; 8min after OG(p&lt;0.001), 12min after LMM(p&lt;0.02). GLP-1; 12min after OG(p&lt;0.01), 10min after LMM (p&lt;0.01).. Insulin; 12min after LMM(p=0.02) and OG(p=0.002). C-peptide; 12min after OG(p=0.002) and LMM(p=0.04). Conclusions Early postprandial hormone responses show characteristic differences with regards to timing and amplitude, but also great individual differences. This should be considered when interpreting mean responses and designing study protocols. ClinicalTrials.gov number NCT03543423.


2021 ◽  
Vol 10 (8) ◽  
pp. 1726
Author(s):  
Leonardo Zoccante ◽  
Michele Marconi ◽  
Marco Luigi Ciceri ◽  
Silvia Gagliardoni ◽  
Luigi Alberto Gozzi ◽  
...  

Equine-assisted activities and therapies (EAAT) have been suggested to improve adaptive behavior, and possibly motor function, in autism spectrum disorder (ASD). This study investigated the effects of EAAT on adaptive behavior and motor function in 15 children with ASD (13 males) aged 7–15 years as well as the impact of EAAT on the magnitude of stress in the parent–child system and the evolution in the child interaction with both the trained therapist and the therapeutic animal through the 20 weekly sessions of EAAT. EAAT were associated with greater adaptive behavior and coordination (all p ≤ 0.01) as well as a progressive improvement in the child’s abilities to respond to the increasing complexity of such form of positive behavioral support (all p < 0.001). However, EAAT did not prove to be effective in reducing parental distress. Collectively, preliminary evidence presented here may have important public health implications and gives reason to hope that EAAT could possibly be an effective option in ASD, warranting further investigation of its potential benefits in clinical trials among larger samples.


2021 ◽  
Author(s):  
Carsten T. Herz ◽  
Johanna M. Brix ◽  
Bernhard Ludvik ◽  
Guntram Schernthaner ◽  
Gerit-Holger Schernthaner

Abstract Purpose Dipeptidyl peptidase 4 (DPP4) is expressed and secreted by adipocytes. DPP4 induces insulin resistance independently of its effect on glucagon-like peptide 1, thus it is conceivable that DPP4 directly contributes to metabolic dysfunction in patients with morbid obesity. The aim of this study was to investigate the impact of weight loss induced by bariatric surgery on DPP4 activity, and whether these changes are associated with improvements in markers of metabolic dysfunction and fatty liver disease. Materials and Methods We included 68 non-diabetic patients who underwent bariatric surgery. Serum DPP4 activity was measured using a fluorogenic substrate before and after surgery. Results Results: After a median follow-up period of 12 (IQR 11-17) months, median serum DPP4 activity decreased from 230 (IQR: 194-273) to 193 (164-252) pmol/min (p=0.012). The decrease in DPP4 activity was significantly correlated with decreases in BMI, improved cholesterol levels, reduced hepatic injury markers as well as improved post-prandial insulin sensitivity. After multivariable adjustment, ΔDPP4 activity remained significantly associated with Δcholesterol (beta=0.341, p=0.025), ΔLDL cholesterol (beta=0.350, p=0.019), Δgamma-glutamyltransferase (beta=0.323, p=0.040) and ΔMatsuda index (beta=-0.386, p=0.045). Conclusion We demonstrated that weight loss induced by bariatric surgery results in decreased circulating DPP4 activity beyond the initial phase of weight loss. The associations between decreased DPP4 activity and improved cholesterol levels as well as hepatic injury markers point towards pleiotropic effects of DPP4 beyond glucose metabolism which warrant further investigation.


2010 ◽  
Vol 38 (5) ◽  
pp. 1261-1269 ◽  
Author(s):  
Adam M. Deane ◽  
Marianne J. Chapman ◽  
Robert J. L. Fraser ◽  
Matthew J. Summers ◽  
Antony V. Zaknic ◽  
...  

2018 ◽  
Vol 315 (4) ◽  
pp. E489-E495 ◽  
Author(s):  
Tanya J. Little ◽  
Nada Cvijanovic ◽  
Nicholas V. DiPatrizio ◽  
Donovan A. Argueta ◽  
Christopher K. Rayner ◽  
...  

Intestinal production of endocannabinoid and oleoylethanolamide (OEA) is impaired in high-fat diet/obese rodents, leading to reduced satiety. Such diets also alter the intestinal microbiome in association with enhanced intestinal permeability and inflammation; however, little is known of these effects in humans. This study aimed to 1) evaluate effects of lipid on plasma anandamide (AEA), 2-arachidonyl- sn-glycerol (2-AG), and OEA in humans; and 2) examine relationships to intestinal permeability, inflammation markers, and incretin hormone secretion. Twenty lean, 18 overweight, and 19 obese participants underwent intraduodenal Intralipid infusion (2 kcal/min) with collection of endoscopic duodenal biopsies and blood. Plasma AEA, 2-AG, and OEA (HPLC/tandem mass spectrometry), tumor necrosis factor-α (TNFα), glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) (multiplex), and duodenal expression of occludin, zona-occludin-1 (ZO-1), intestinal-alkaline-phosphatase (IAP), and Toll-like receptor 4 (TLR4) (by RT-PCR) were assessed. Fasting plasma AEA was increased in obese compared with lean and overweight patients ( P < 0.05), with no effect of BMI group or ID lipid infusion on plasma 2-AG or OEA. Duodenal expression of IAP and ZO-1 was reduced in obese compared with lean ( P < 0.05), and these levels related negatively to plasma AEA ( P < 0.05). The iAUC for AEA was positively related to iAUC GIP ( r = 0.384, P = 0.005). Obese individuals have increased plasma AEA and decreased duodenal expression of ZO-1 and IAP compared with lean and overweight subjects. The relationships between plasma AEA with duodenal ZO-1, IAP, and GIP suggest that altered endocannabinoid signaling may contribute to changes in intestinal permeability, inflammation, and incretin release in human obesity.


Diabetes Care ◽  
2013 ◽  
Vol 36 (7) ◽  
pp. 1913-1918 ◽  
Author(s):  
T. Wu ◽  
M. J. Bound ◽  
B. R. Zhao ◽  
S. D. Standfield ◽  
M. Bellon ◽  
...  

2004 ◽  
Vol 286 (2) ◽  
pp. R390-R397 ◽  
Author(s):  
D. N. D'Souza ◽  
Y. Zhang ◽  
F. Garcia ◽  
G. Battaglia ◽  
L. D. Van de Kar

Tryptophan depleting protocols are commonly used to study the role of serotonin in mood disorders. The present study examined the impact of a tryptophan-deficient diet and fluoxetine on the serotonergic regulation of neuroendocrine function and body weight. We hypothesized that the regulation of postsynaptic 5-HT1A receptors is dependent on the levels of 5-HT in the synapse. Rats on a control or a tryptophan-deficient diet received daily injections of saline or fluoxetine (5 or 10 mg·kg-1·day-1 ip) from day 7 to day 21. The tryptophan-deficient diet produced a 41% reduction in the level of 5-HT but no change in the density of [3H]paroxetine-labeled 5-HT transporters. Treatment with fluoxetine inhibited the gain in weight in rats maintained on the control diet. The tryptophan-deficient diet produced a significant loss in body weight that was not significantly altered by treatment with fluoxetine. Treatment with fluoxetine produced a dose-dependent desensitization of hormone responses to injection of the 5-HT1A receptor agonist (±)8-hydroxy-2-(di- n-propylamino)tetralin ((±)8-OH-DPAT). The tryptophan-deficient diet produced an increase in the basal levels of corticosterone but did not alter the basal levels of ACTH or oxytocin. Also, this diet inhibited the magnitude of 8-OH-DPAT-induced increase in plasma levels of ACTH and oxytocin but did not impair the ability of fluoxetine to desensitize the 5-HT1A receptor-mediated increase in plasma hormones. These data suggest that a reserve of 5-HT enables fluoxetine to desensitize postsynaptic 5-HT1A receptors in the hypothalamus. In conclusion, the profound physiological changes induced by tryptophan depletion may complicate the interpretation of studies using this experimental approach.


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