Human Pancreatic Exocrine Response to Nutrients in Health and Disease
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vi1 REVIEW Human pancreatic exocrine response to nutrients in health Gut: first published as 10.1136/gut.2005.065946 on 10 June 2005. Downloaded from and disease J Keller, P Layer ............................................................................................................................... Gut 2005;54(Suppl VI):vi1–vi28. doi: 10.1136/gut.2005.065946 1.0 INTRODUCTION exocrine response to various endogenous stimuli. Optimal digestion and absorption of nutrients This chapter will summarise literature data on requires a complex interaction among motor and pancreatic exocrine response to a normal diet, its secretory functions of the gastrointestinal tract. physical and biochemical properties, and to Digestion of macronutrients is a prerequisite for administration of individual food components absorption and occurs mostly via enzymatic in healthy humans with respect to total pan- hydrolysis. In this context, pancreatic enzymes, creatic secretion, secretion of individual in particular lipase, amylase, trypsin, and chy- enzymes, ratios of enzymes, intraluminal pH motrypsin, play the most important role but and bicarbonate and bile acid secretion. several brush border enzymes as well as other pancreatic and extrapancreatic enzymes also 2.2 Pancreatic response to a normal diet participate in macronutrient digestion. The cru- In the fasting state, human pancreatic exocrine cial importance of pancreatic exocrine function is secretion is cyclical and closely correlated with reflected by the detrimental malabsorption in upper gastrointestinal motility (fig 1).16 patients with untreated pancreatic exocrine Ingestion of a regular meal disrupts this inter- insufficiency, which is a typical complication of, digestive pattern within a few minutes and for example, chronic pancreatitis.1–4 induces postprandial enzyme secretion instead, Comprehensive knowledge about the physio- which has also been shown to follow a consistent logical pancreatic exocrine response to normal pattern: enzyme delivery into the duodenum diets and to individual food components and increases rapidly and reaches maximal values about alterations in pancreatic exocrine insuffi- within the first postprandial hour,7–10 or even ciency is necessary to administer a pancreatic within 20–30 minutes postprandially.11–13 enzyme preparation which imitates physiological Following peak output, enzyme secretion conditions closely. Although many efforts have decreases to a fairly stable secretory rate before http://gut.bmj.com/ been made to substitute for pancreatic exocrine decreasing again after about 3–4 hours postpran- insufficiency by specially designed pancreatic dially to finally reach the interdigestive range at enzyme preparations, these still have several the end of the digestive period (fig 2).7–13 The disadvantages compared with physiological degree and the duration of the digestive enzyme enzyme secretion. In particular lipid absorption response are determined by the caloric con- is not completely normalised in most patients.5 tent,13 14 nutrient composition, and physical As a basis for a better understanding of properties of the meal. pancreatic exocrine function in health and In addition, the route or site of administration on September 27, 2021 by guest. Protected copyright. disease this review will first summarise literature of nutrients strongly influences pancreatic data on pancreatic exocrine response to a normal enzyme responses: oral and duodenal application diet and to administration of individual food of a complex formula initiate similar increases in components in healthy humans. The next chap- secretion of amylase, lipase, and trypsin.15 In ter will focus on pancreatic responses to a normal contrast, jejunal infusion of nutrients has lower diet and to administration of individual food stimulatory potency than duodenal (about components in patients with pancreatic diseases, 25%)916 while ileal nutrient perfusion inhibits in particular chronic pancreatitits, but also in enzyme secretion (compare 2.2.9).17–20 Moreover, patients with other pancreatic and non-pancrea- intraduodenal administration of an elemental tic diseases which are associated with intralum- formula equicaloric with the complex formula inal lack of pancreatic enzymes, for instance halved the stimulation of enzyme secretion.15 coeliac disease and diabetes mellitus. Other evidence of pancreatic involvement and dysfunc- 2.2.1 Influence of the caloric content tion in these diseases will also be discussed, Duodenal nutrient exposure is the dominant See end of article for particularly if sufficient data on endogenously stimulatory mechanism for the postprandial authors’ affiliations stimulated pancreatic secretion are lacking. ....................... enzyme response. In order to permanently Correspondence to: Dr J Keller, Israelitic 2.0 SECRETORY RESPONSE OF THE Abbreviations: CCK, cholecystokinin; CFTR, cystic Hospital, University of EXOCRINE PANCREAS TO NUTRIENTS IN fibrosis transmembrane regulator; DPPHR, duodenum Hamburg, Orchideenstieg HEALTHY HUMANS preserving pancreatic head resection; ERCP, endoscopic 14, D-22297 Hamburg, 2.1 Introduction retrograde cholangiopancreatography; GLP-1, glucagen- Germany; [email protected] like peptide-1; IDDM, insulin dependent diabetes mellitus; The healthy human pancreas adopts exocrine MMC, migrating motor complex; NIDDM, non-insulin Accepted 29 March 2005 secretion to nutrient ingestion and there are dependent diabetes mellitus; PPPD, pylorus preserving ....................... numerous studies investigating pancreatic pancreatoduodenectomy. www.gutjnl.com vi2 Keller, Layer 800 * Test meal 600 700 Gut: first published as 10.1136/gut.2005.065946 on 10 June 2005. Downloaded from 600 500 500 400 * 400 300 300 200 Amylase (U/min) 200 % of basal100 secretion 100 0 0 300 30 60 90 120 150 180 210 240 Phase I Phase II Phase III Postprandial minutes Figure 1 Interdigestive amylase output in healthy volunteers during Figure 2 Digestive pancreatic enzyme response to a regular meal. daytime. Enzyme output is cyclical: it is associated with intestinal motility Enzyme delivery into the duodenum increases rapidly and reaches and is higher during phases II and III compared with phase I (*p,0.05 v maximal values within the first postprandial hour or even within phase I).322 20–30 minutes postprandially. Following peak output, enzyme secretion decreases to almost stable secretory rates at lower levels until about 3–4 hours postprandially depending on the size of the meal. The inter- stimulate pancreatic enzyme secretion and to convert the digestive range is reached again at the end of the digestive period.7–13 interdigestive secretory pattern to the fed pattern in response to a mixed meal, intraduodenal nutrient loads of about 2.2.3 Influence of physical properties 1 kcal/min are required. Thus, the cyclical interdigestive Apart from caloric content and nutrient composition, pattern was clearly preserved with duodenal nutrient loads of physical properties of a meal also affect pancreatic secretion. 0.36 kcal/min, independently of whether proteins, carbohy- Enzyme response to a solid meal is more sustained compared 21 drates, or lipids were perfused. However, a recent study has with an identical meal which has been homogenised.8 This is shown that even higher duodenal nutrient delivery rates partly due to slower gastric emptying of the solid compared (1.5–2.67 kcal/min) did not completely abolish cycles of with the homogenised meal which leads to prolonged enzyme secretion but modulated cycles by increasing the stimulation of enzyme output. In addition, increased gastric 22 nadir instead. Duodenal perfusion rates in the latter study acid secretion and, consequently, increased duodenal acid were chosen to imitate physiological gastric emptying rates of delivery in response to a solid meal may also cause a higher 2–3 kcal/min following ingestion of a normal meal in healthy pancreatic secretory response.8 23 humans. With meals ranging from about 200–500 kcal, a Due to better applicability in intubation studies many positive correlation between postprandial amylase secretion investigators have used semiliquid, homogenised meals and and meal energy density was observed as a result of initially have shown an overall similar pattern for postprandial higher and also longer lasting output of amylase after high pancreatic enzyme secretion compared with solid meals with 13 http://gut.bmj.com/ energy meals. By contrast, when healthy subjects ingested maximal secretory rates early postprandially, lower, yet stable three meals per day containing either 20, 30, or 40 kcal/kg, or slowly declining secretion for about 2–3 hours followed by maximal enzyme response was already achieved by the a fast decrease into the interdigestive range.9 18 25–27 14 20 kcal/kg diet (which means 1500 kcal per day or 500 kcal Other physical properties of a meal such as volume, per meal in a subject with 75 kg bodyweight). Therefore, osmolality, and temperature may also influence pancreatic meals containing about 500 kcal seem to be sufficient to enzyme secretion, either directly or by altering gastric induce maximal enzyme response. However, there is a emptying. Dooley et al report a stepwise increase in pancreatic positive correlation between the duration of digestive amylase and bicarbonate secretion in response to duodenal on September 27, 2021 by guest. Protected copyright. 14 secretion and nutrient content also with high caloric meals, perfusion with increasing flow rates of saline (0.2 to 3.2