Role of intraduodenal proteases in plasma cholecystokinin and pancreaticobiliary responses to protein and amino acids

doi:10.1053/gast.1996.v110.pm8566605

Gastroenterology

Volume 110, Issue 2, February 1996, Pages 567-575

https://doi.org/10.1053/gast.1996.v110.pm8566605 Get rights and content

Abstract

BACKGROUND & AIMS: The role of small intestinal proteolytic activity in the regulation of upper gastrointestinal function in humans is poorly understood. The aim of this study was to determine the importance of proteolytic activity for protein- or amino acid-induced cholecystokinin release and pancreaticobiliary secretion. METHODS: In 9 healthy subjects, saline was perfused intraduodenally for 3 hours either with or without the synthetic protease inhibitor camostate. During the last hour, albumin or amino acids in the same molecular composition as albumin were also perfused. RESULTS: Perfusion with camostate, in concentrations that abolished intraduodenal proteolytic activity, had no effect on unstimulated plasma cholecystokinin concentrations or gallbladder emptying, but markedly (P < 0.05) increased unstimulated pancreatic enzyme output. Perfusion with protein distinctly stimulated cholecystokinin release, gallbladder emptying, and pancreatic enzyme output (P < 0.05). Perfusion with camostate resulted in significantly lower protein-stimulated plasma cholecystokinin, gallbladder, and pancreatic enzyme responses (P < 0.05). Perfusion with amino acids also stimulated plasma cholecystokinin, gallbladder emptying, and pancreatic enzyme output (P < 0.05). Camostate did not inhibit these values. CONCLUSIONS: This study shows that appropriate digestion of protein is required to stimulate plasma cholecystokinin release, gallbladder emptying, and pancreatic enzyme secretion in humans. (Gastroenterology 1996 Feb;110(2):567-75)

References (0)

Cited by (42)

Effects of intraduodenal infusion of lauric acid and L-tryptophan, alone and combined, on glucoregulatory hormones, gastric emptying and glycaemia in healthy men
2022, Metabolism: Clinical and Experimental
Citation Excerpt :
Moreover, nutrient ‘preloads’, e.g. 30 mL olive oil or 55 g whey protein, when consumed ~30 min before a carbohydrate meal, slow gastric emptying, stimulate GLP-1 and attenuate the postprandial rise in glucose [8,9]. These effects, however, necessitate administration of relatively large caloric loads (~220–270 kcal), probably because of the time required for digestion of fat and protein to release fatty acids [10,11] and amino acids [12,13], required to elicit the effects. Among the products of fat and protein digestion, the fatty acid, lauric acid (‘C12’), and the amino acid, L-tryptophan (‘TRP’), appear to have particularly potent effects [14,15].
In healthy men, intraduodenal administration of the fatty acid, lauric acid (‘C12’) and the amino acid, L-tryptophan (‘TRP’), at loads that individually do not affect energy intake, reduce energy intake substantially when combined. C12 and TRP may also stimulate cholecystokinin and glucagon-like peptide-1 (GLP-1), which both slow gastric emptying, a key determinant of postprandial blood glucose. Accordingly, combination of C12 and TRP has the potential to reduce post-meal glycaemia more than either nutrient alone.
Twelve healthy, lean men (age (mean ± SD): 28 ± 7 years) received, on 4 separate occasions, 45-min intraduodenal infusions of C12 (0.3 kcal/min), TRP (0.1 kcal/min), C12 + TRP (0.4 kcal/min), or 0.9% saline (control), in a randomised, double-blind fashion. 30 min after commencement of the infusion a mixed-nutrient drink was consumed and gastric emptying measured (¹³C breath-test) for 3 h. Blood samples were obtained at baseline, in response to treatments alone, and for 2 h post-drink for measurements of plasma glucose, cholecystokinin, GLP-1, C-peptide, insulin and glucagon. ‘Early’ (first 30 min) and ‘overall’ glycaemic and hormone responses were evaluated.
C12 + TRP and C12 delayed the rise in, but did not affect the overall glycaemic response to the drink, compared with control and TRP (all P < 0.05). C12 + TRP slowed gastric emptying compared with control and TRP (both P < 0.005), and C12 non-significantly slowed gastric emptying compared with control (P = 0.090). C12 + TRP and C12 delayed the rise in C-peptide and insulin, and also stimulated CCK and glucagon, compared with control and TRP (all P < 0.05). Only C12 + TRP stimulated early and overall GLP-1 compared with control (P < 0.05).
In healthy men, C12 + TRP and C12, in the loads administered, had comparable effects to delay the rise in glucose following a nutrient drink, probably primarily by slowing of gastric emptying, as a result of CCK and GLP-1 stimulation, while TRP had no effect.
The nutritional quality of eggs
2011, Improving the Safety and Quality of Eggs and Egg Products
Scientific evidence and consumer awareness of the importance of diet in combination with a healthy lifestyle has led to an increased focus on the nutritional evaluation of certain foods such as eggs. Nutritional evaluation includes the nutrient quantification (per 100 g or per portion) of the food, which conveys the contribution of the nutrient content to an individual’s daily supply and the role played by the food as part of a balanced and healthy diet. With this in mind, this chapter describes the function of certain nutrients, taking into account beneficial or adverse effects of an average intake level. Based on this evaluation, the appropriate use of enrichment to improve the nutritional quality of eggs is discussed.
Control of pancreatic secretion in humans
2010, Advances in Medical Sciences
Citation Excerpt :
Whether the meal was given as mixed amino acids or protein solutions, the pancreatobiliary secretions were comparable [76]. However, for maximal pancreatic response to dietary protein, an adequate protein digestion is a prerequisite [83] and among the stimulatory, potency mostly depends on specific amino acids including: phenylalanine, valine, methionine and tryptophane [84]. The quantitative differences in pancreatic enzyme output are influenced by the quantity and quality of food delivered to the intestine; CCK released by the different food components could be a major factor in the overall pancreatic secretory response.
Studies on the control of pancreatic secretion in humans of all ages have been a difficult task over the years because of patients’ availability and ethic committee rules. Nevertheless, studies were performed and the objectives of this review are to summarize our knowledge on the development of secretory process in newborns, on the different phases of the pancreatic responses to a meal, on the pancreatic responses to the different components of the diet, on the mechanisms involved in the control of the pancreatic responses, and finally on the receptors involved in these controls.
Persistent decreased plasma cholecystokinin levels in celiac patients under gluten-free diet: Respective roles of histological changes and nutrient hydrolysis
2002, Regulatory Peptides
Celiac disease is associated with impaired cholecystokinin (CCK) release. The mechanism by which CCK release is impaired is poorly understood and seems to be related to the mucosal atrophy or to decreased stimulation due to reduced intraduodenal nutrient hydrolysis. The aims of our study were to evaluate basal and postprandial CCK in celiac patients presenting with distinctive types of mucosal lesions (normal, infiltrative and atrophic), and to study the role of protein hydrolysis on CCK release. Plasma CCK was measured in 20 celiac patients (normal mucosa: n=6; infiltrative type: n=6; atrophic type=8) and 9 controls, before and after ingestion of a polymeric or a semi-elemental meal. Significant decreases in basal CCK plasma (B 0.6 [95% CI, 0.3–1.3] pmol/l; p<0.003) and postprandial CCK area under curve (AUC 34 [19–61] pmol/l×120 min, p<0.0001) were observed in patients with an atrophic mucosa compared with treated patients (B 1.6 [1.0–2.4] pmol/l, AUC 267 [172–414] pmol/l×120 min) or healthy volunteers (B 1.0 [0.7–1.4] pmol/l, AUC 186 [131–264] pmol/l×120 min). A significant defective CCK release was also observed in patients with an infiltrative type: B 0.4 [0.2–0.7] pmol/l and AUC 56 [31–101] pmol/l×120 min; p<0.0001. Administration of a semi-elemental diet did not correct the defective CCK release. In conclusion, the decreased CCK levels observed in celiac patients are not strictly related to the mucosal atrophy but rather to the lymphocytic infiltrate. Administration of a predigested meal did not correct the impaired CCK release. Some inhibitory mechanism could be involved in the CCK cell dysfunction observed in celiac patients presenting with lesser degrees of disease activity.
Anorexia and malnutrition in patients with obstructive jaundice
2002, Nutrition
Impaired pancreatic secretion in severely malnourished patients is a consequence of primary pancreatic dysfunction
2001, Nutrition
Severe undernutrition has been associated with reduced secretions of gastric acid and pancreatic enzymes. This may be the result of an impaired gut mucosal response to food and primary gastric parietal and pancreatic acinar cell secretory dysfunction as a consequence of the poor nutritional state. To investigate the relative contributions of these factors, severely undernourished patients underwent enteral-meal–stimulated (ES; n = 7) or intravenous hormone (pentagastrin and cholecystokinin-8)–stimulated (HS; n = 12) gastric acid and pancreatic enzyme secretion before and after a period of nutritional support. Results were evaluated in comparison with normal healthy control subjects (ES = 7, HS = 10). In the control subjects, enteral-meal and cholecystokinin-8 stimulation resulted in similar outputs of the pancreatic enzymes amylase (2213 versus 2305 U/h), lipase (84.93 versus 118.6 U/h), and trypsin (498.9 versus 341.4 U/h), whereas acid output was significantly lower in the ES group (10.90 versus 25.53 mEq/h; P < 0.01). Compared with controls, malnourished groups had significantly reduced secretions of amylase (ES = 870.1 U/h, HS = 686.5 U/h; P < 0.02), lipase (ES = 30.68 U/h, HS = 25.96 U/h; P < 0.02), and trypsin (ES = 175.6 U/h, HS = 109.3 U/h; P < 0.01). The response to enteral-meal or CCK-8 stimulation was comparable. Gastric acid was similarly reduced in the undernourished patients (ES = 4.39 mEq/h, HS = 5.04 mEq/h; P < 0.01). After refeeding, secretion of amylase (ES = 2351 U/h, HS = 2228 U/h) and lipase (ES = 58.83 U/h, HS = 84.91 U/h) improved to levels not significantly different from controls, whereas trypsin (ES = 226.4 U/h, HS = 213.1 U/h; P < 0.03) and acid secretion (ES = 3.52 mEq/h, HS = 11.85 mEq/h; P < 0.01) remained significantly impaired. Severe undernutrition was associated with primary gastric parietal and pancreatic acinar cell dysfunction, which, at least in the case of pancreatic enzymes, appeared to be the determining factor controlling secretion in these patients.

View all citing articles on Scopus

View full text