Regulation of gastric and pancreatic lipase secretion by CCK and cholinergic mechanisms in humans

Gastric lipase (HGL) contributes significantly to fat digestion. However, little is known about its neurohormonal regulation in humans. We studied the role of CCK and cholinergic mechanisms in the postprandial regulation of HGL and pancreatic lipase (HPL) secretion in six healthy subjects. Gastric emptying of a mixed meal and outputs of HGL, pepsin, acid, and HPL were determined with a double-indicator technique. Three experiments were performed in random order: intravenous infusion of 1) placebo, 2) low-dose atropine (5 micrograms.kg-.h-1), and 3) the CCK-A receptor antagonist loxiglumide (22 mumol.kg-.h-1). Atropine decreased postprandial outputs of HGL, pepsin, gastric acid, and HPL (P < 0.03) while slowing gastric emptying (P < 0.05). Loxiglumide markedly increased the secretion of HGL, pepsin, and acid while distinctly reducing HPL outputs and accelerating gastric emptying (P < 0.03). Plasma CCK and gastrin levels increased during loxiglumide infusion (P < 0.03). Atropine enhanced gastrin but not CCK release. Postprandial HGL, pepsin, and acid secretion are under positive cholinergic but negative CCK control, whereas HPL is stimulated by cholinergic and CCK mechanisms. We conclude that CCK and cholinergic mechanisms have an important role in the coordination of HGL and HPL secretion to optimize digestion of dietary lipids in humans.

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Inhibition of gastric emptying by acarbose is correlated with GLP-1 response and accompanied by CCK release

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.281.3.g752 ◽

2001 ◽

Vol 281 (3) ◽

pp. G752-G763 ◽

Cited By ~ 68

Author(s):

Feruze Y. Enç ◽

Neşe I˙meryüz ◽

Levent Akin ◽

Turgut Turoğlu ◽

Fuat Dede ◽

...

Keyword(s):

Gastric Emptying ◽

Peptide Yy ◽

Area Under The Curve ◽

Gut Hormones ◽

Random Order ◽

Mixed Meal ◽

Carbohydrate Absorption ◽

Plasma Response ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

We investigated the effect of acarbose, an α-glucosidase and pancreatic α-amylase inhibitor, on gastric emptying of solid meals of varying nutrient composition and plasma responses of gut hormones. Gastric emptying was determined with scintigraphy in healthy subjects, and all studies were performed with and without 100 mg of acarbose, in random order, at least 1 wk apart. Acarbose did not alter the emptying of a carbohydrate-free meal, but it delayed emptying of a mixed meal and a carbohydrate-free meal given 2 h after sucrose ingestion. In meal groups with carbohydrates, acarbose attenuated responses of plasma insulin and glucose-dependent insulinotropic polypeptide (GIP) while augmenting responses of CCK, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). With mixed meal + acarbose, area under the curve (AUC) of gastric emptying was positively correlated with integrated plasma response of GLP-1 ( r = 0.68 , P < 0.02). With the carbohydrate-free meal after sucrose and acarbose ingestion, AUC of gastric emptying was negatively correlated with integrated plasma response of GIP, implying that prior alteration of carbohydrate absorption modifies gastric emptying of a meal. The results demonstrate that acarbose delays gastric emptying of solid meals and augments release of CCK, GLP-1, and PYY mainly by retarding/inhibiting carbohydrate absorption. Augmented GLP-1 release by acarbose appears to play a major role in the inhibition of gastric emptying of a mixed meal, whereas CCK and PYY may have contributory roles.

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Orlistat accelerates gastric emptying and attenuates GIP release in healthy subjects

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.90209.2008 ◽

2009 ◽

Vol 296 (3) ◽

pp. G482-G489 ◽

Cited By ~ 17

Author(s):

Feruze Yılmaz Enç ◽

Tunç Öneş ◽

H. Levent Akın ◽

Fuat Dede ◽

H. Turgut Turoğlu ◽

...

Keyword(s):

Gastric Emptying ◽

Healthy Subjects ◽

Weight Control ◽

Peptide Yy ◽

Area Under The Curve ◽

Random Order ◽

Gut Peptides ◽

Mixed Meal ◽

Moderate Energy ◽

Pellet Form

Orlistat, an inhibitor of digestive lipases, is widely used for the treatment of obesity. Previous reports on the effect of orally ingested orlistat together with a meal on gastric emptying and secretion of gut peptides that modulate postprandial responses are controversial. We investigated the effect of ingested orlistat on gastric emptying and plasma responses of gut peptides in response to a solid mixed meal with a moderate energy load. In healthy subjects, gastric emptying was determined using scintigraphy and studies were performed without and with 120 mg of orlistat in pellet form in random order. Orlistat shortened t lag and t half and decreased the area under the gastric emptying curve. Orlistat significantly attenuated the secretion of glucose-dependent insulinotropic polypeptide (GIP) but did not alter the plasma responses of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP), and insulin. There was no peptide YY (PYY) response. Area under the curve of gastric emptying was positively correlated with integrated secretion of GIP ( r = 0.786) in orlistat and was negatively correlated with integrated plasma response of GLP-1 ( r = −0.75) in control experiments, implying that inhibition of fat absorption modifies determinants of gastric emptying of a meal. Orlistat administered similar to its use in obesity treatment accelerates gastric emptying of a solid mixed meal with a moderate energy load and profoundly attenuates release of GIP without appreciably altering plasma responses of CCK, GLP-1, and PP. Since GIP is being implemented in the development of obesity, its role in weight control attained by orlistat awaits further investigation.

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Gastric Sensory and Motor Functions and Energy Intake in Health and Obesity—Therapeutic Implications

Nutrients ◽

10.3390/nu13041158 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1158

Author(s):

Lizeth Cifuentes ◽

Michael Camilleri ◽

Andres Acosta

Keyword(s):

Energy Consumption ◽

Gastric Emptying ◽

Food Intake ◽

Gastric Volume ◽

Obesity Management ◽

Bariatric Endoscopy ◽

Motor Functions ◽

Therapeutic Implications ◽

Intestinal Functions

Sensory and motor functions of the stomach, including gastric emptying and accommodation, have significant effects on energy consumption and appetite. Obesity is characterized by energy imbalance; altered gastric functions, such as rapid gastric emptying and large fasting gastric volume in obesity, may result in increased food intake prior to reaching usual fullness and increased appetite. Thus, many different interventions for obesity, including different diets, anti-obesity medications, bariatric endoscopy, and surgery, alter gastric functions and gastrointestinal motility. In this review, we focus on the role of the gastric and intestinal functions in food intake, pathophysiology of obesity, and obesity management.

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Mechanistic role of antioxidants in rescuing delayed gastric emptying in high fat diet induced diabetic female mice

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2021.111370 ◽

2021 ◽

Vol 137 ◽

pp. 111370

Author(s):

Chethan Sampath ◽

Derek Wilus ◽

Mohammad Tabatabai ◽

Michael L. Freeman ◽

Pandu R. Gangula

Keyword(s):

Gastric Emptying ◽

High Fat Diet ◽

Delayed Gastric Emptying ◽

High Fat ◽

Female Mice

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Effects of mixed meal tolerance test on gastric emptying, glucose and lipid homeostasis in obese nonhuman primates

Scientific Reports ◽

10.1038/s41598-021-91027-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kamal Albarazanji ◽

Andrea R. Nawrocki ◽

Bin Gao ◽

Xiaoli Wang ◽

Yixin Wang ◽

...

Keyword(s):

Gastric Emptying ◽

Glucose Homeostasis ◽

Plasma Glucose ◽

Nonhuman Primates ◽

Surrogate Marker ◽

Tolerance Test ◽

Mixed Meal ◽

C Peptide ◽

Meal Tolerance Test ◽

Mixed Meal Tolerance Test

AbstractMeal ingestion elicits a variety of neuronal, physiological and hormonal responses that differ in healthy, obese or diabetic individuals. The mixed meal tolerance test (MMTT) is a well-established method to evaluate pancreatic β-cell reserve and glucose homeostasis in both preclinical and clinical research in response to calorically defined meal. Nonhuman primates (NHPs) are highly valuable for diabetic research as they can naturally develop type 2 diabetes mellitus (T2DM) in a way similar to the onset and progression of human T2DM. The purpose of this study was to investigate the reproducibility and effects of a MMTT containing acetaminophen on plasma glucose, insulin, C-peptide, incretin hormones, lipids, acetaminophen appearance (a surrogate marker for gastric emptying) in 16 conscious obese cynomolgus monkeys (Macaca fascicularis). Plasma insulin, C-peptide, TG, aGLP-1, tGIP, PYY and acetaminophen significantly increased after meal/acetaminophen administration. A subsequent study in 6 animals showed that the changes of plasma glucose, insulin, C-peptide, lipids and acetaminophen were reproducible. There were no significant differences in responses to the MMTT among the obese NHPs with (n = 11) or without (n = 5) hyperglycemia. Our results demonstrate that mixed meal administration induces significant secretion of several incretins which are critical for maintaining glucose homeostasis. In addition, the responses to the MMTTs are reproducible in NHPs, which is important when the MMTT is used for evaluating post-meal glucose homeostasis in research.

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Reflux aspiration associated with oesophageal dysmotility but not delayed liquid gastric emptying

Digestive Diseases ◽

10.1159/000514108 ◽

2020 ◽

Author(s):

Oleksandr Khoma ◽

Maite Jeanne Mendu ◽

Amita Nandini Sen ◽

Hans Van der Wall ◽

Gregory Leighton Falk

Keyword(s):

Gastric Emptying ◽

Reflux Disease ◽

Inclusion Criteria ◽

Treatment Resistant ◽

Oesophageal Motility ◽

Oesophageal Manometry ◽

Oesophageal Dysmotility ◽

The Relationship ◽

Clinical Subtype

Abstract Introduction Severe oesophageal dysmotility is associated with treatment resistant reflux and pulmonary reflux aspiration. Delayed solid gastric emptying (SGE) has been associated with oesophageal dysmotility, however the role of delayed liquid gastric emptying (LGE) in the pathophysiology of severe reflux disease remains unknown. The purpose of this study is to examine the relationship between delayed LGE, reflux aspiration and oesophageal dysmotility. Methods Data was extracted from a prospectively populated database of patients with severe treatment resistant gastro-oesophageal reflux disease (GORD). All patients with validated reflux aspiration scintigraphy (RASP) and oesophageal manometry were included in the analysis. Patients were classified by predominant clinical subtype as gastro-oesophageal (GOR) or laryngo-pharyngeal (LPR) reflux. LGE time of 22 minutes or longer was considered delayed. Results Inclusion criteria were met by 631 patients. Normal LGE time was found in 450 patients, whilst 181 had evidence of delayed LGE. Mean liquid half-clearance was 22.81min. Refux aspiration was evident in 240 patients (38%). Difference in the aspiration rates between delayed LGE (42%) and normal LGE (36%) was not significant (p=0.16). Severe ineffective oesophageal motility (IOM) was found in 70 patients (35%) and was independent of LGE time. Severe IOM was strongly associated with reflux aspiration (p<0.001). GOR dominant symptoms were more common in patients with delayed LGE (p=0.03). Conclusion Severe IOM was strongly associated with reflux aspiration. Delayed LGE is not associated with reflux aspiration or severe IOM. Delayed LGE is more prevalent in patients presenting with GOR dominant symptoms.

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