Comparison of the Effect of Single and Repeated Administrations of a Protease Inhibitor (Camostate) on Pancreatic Secretion in Man

Adler, Guido; Müllenhoff, A.; Bozkurt, T; Göke, Burkhard; Koop, Irmtraut; Arnold, R.

doi:10.3109/00365528809103961

Cited by 23 publications

(2 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overall, the data are consistent with the notions that (a) intraduodenal trypsin and chymotrypsin both suppress human pancreatic secretion, (b) that suppression is minimal in advanced pancreatic insufficiency and (c) patients who fail to suppress pancreatic secretion often do not experience pain relief with enzyme supplementation (Slaff et al 1984). The data regarding control of pancreatic secretion in human are consistent with several distinct feedback pathways, one mediated by proteases (e.g., trypsin/chymotrypsin) (Adler et al 1988a, b; Ebbehoj et al 1990; Liener et al 1988) and another by acetylcholine (Owyang et al 1986b).…”

Section: Chronic Pancreatitismentioning

confidence: 68%

Rational Use of Pancreatic Enzymes for Pancreatic Insufficiency and Pancreatic Pain

Ketwaroo

Graham

2019

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

We describe the rational use of enteric coated and unprotected replacement pancreatic enzymes for treatment of malabsorption due to pancreatic insufficiency and for pancreatic pain. Enteric coated formulations mix poorly with food allowing separation of enzymes and nutrients when emptying from the stomach. The site of dissolution of the enteric coating in the intestine is also unpredictable and enzymes may not be released until the distal intestine. Together, these barriers result in the lack of dose-response such that the strategy of increasing the dosage following a suboptimal effect is often ineffective. The ability to maintain the intragastric pH ≥4 with the combination of proton pumpinhibitors and antacids suggests that it should be possible to reliably obtain a good response with uncoated enzymes. We also discuss the recognition, treatment and prevention of nutritional deficiencies associated with pancreatic insufficiency and recommend a test and treat strategy to identify and resolve nutritional deficits. Finally, we focus on mechanisms causing pain that may be amenable to therapy with pancreatic enzymes. Pain due to malabsorbed digestive contents can be prevented by successful therapy of malabsorption. Feedback inhibition of endogenous pancreatic secretion can prevent pain associated with pancreatic secretion but requires use of non-enteric coated formulations.

show abstract

Section: Chronic Pancreatitismentioning

confidence: 68%

Rational Use of Pancreatic Enzymes for Pancreatic Insufficiency and Pancreatic Pain

Ketwaroo

Graham

2019

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

show abstract

“…Alternatively, trypsin inhibition in an amino acid-rich (Ensure) diet should not result in a liver ISR response. For example a CCK-mediated pancreatic response to amino acid intake was absent (compared with protein) during intraduodenal CS in humans (1). Finally, the site of action of circulating FGF21 is thought to primarily be on central nervous system (CNS) ␤klothoR1c (6,42).…”

Section: Discussionmentioning

confidence: 99%

Intestinal serine protease inhibition increases FGF21 and improves metabolism in obese mice

Al-Barazanji

Jennis

Cavanaugh

et al. 2019

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Trypsin is the major serine protease responsible for intestinal protein digestion. An inhibitor, camostat (CS), reduced weight gain, hyperglycemia, and dyslipidemia in obese rats; however, the mechanisms for these are largely unknown. We reasoned that CS creates an apparent dietary protein restriction, which is known to increase hepatic fibroblast growth factor 21 (FGF21). Therefore, metabolic responses to CS and a gut-restricted CS metabolite, FOY-251, were measured in mice. Food intake, body weight, blood glucose, branched-chain amino acids (LC/MS), hormone levels (ELISA), liver pathology (histology), and transcriptional changes (qRT-PCR) were measured in ob/ob, lean and diet-induced obese (DIO) C57BL/6 mice. In ob/ob mice, CS in chow (9–69 mg/kg) or FOY-251 (46 mg/kg) reduced food intake and body weight gain to a similar extent as pair-fed mice. CS decreased blood glucose, liver weight, and lipidosis and increased FGF21 gene transcription and plasma levels. In lean mice, CS increased liver FGF21 mRNA and plasma levels. Relative to pair feeding, FOY-251 also increased plasma FGF21 and induced liver FGF21 and integrated stress response (ISR) transcription. In DIO mice, FOY-251 (100 mg/kg po) did not alter peak glucose levels but reduced the AUC of the glucose excursion in response to an oral glucose challenge. FOY-251 increased plasma FGF21 levels. In addition to previously reported satiety-dependent (cholecystokinin-mediated) actions, intestinal trypsin inhibition engages non-satiety-related pathways in both leptin-deficient and DIO mice. This novel mechanism improves metabolism by a liver-integrated stress response and increased FGF21 expression levels in mice. NEW & NOTEWORTHY Trypsin inhibitors, including plant-based consumer products, have long been associated with metabolic improvements. Studies in the 1980s and 1990s suggested this was due to satiety hormones and caloric wasting by loss of protein and fatty acids in feces. This work suggests an entirely new mechanism based on the lower amounts of digested protein available in the gut. This apparent protein reduction may cause beneficial metabolic adaptation by the intestinal-liver axis to perceived nutrient stress.

show abstract

Anticarcinogenic Activity of Protease Inhibitors Overview

Kennedy

1993

Protease Inhibitors as Cancer Chemopreventive Agents

View full text Add to dashboard Cite

Comparison of the Effect of Single and Repeated Administrations of a Protease Inhibitor (Camostate) on Pancreatic Secretion in Man

Cited by 23 publications

References 10 publications

Rational Use of Pancreatic Enzymes for Pancreatic Insufficiency and Pancreatic Pain

Rational Use of Pancreatic Enzymes for Pancreatic Insufficiency and Pancreatic Pain

Intestinal serine protease inhibition increases FGF21 and improves metabolism in obese mice

Anticarcinogenic Activity of Protease Inhibitors Overview

Contact Info

Product

Resources

About