Pancreatic Digestive Enzyme Secretion Research Articles

Exocrine pancreatic insufficiency as a possible predictor of pancreatic cancer development.

679 Background: Chronic and acute pancreatitis are established risk factors for pancreatic cancer. Chronic pancreatitis and pancreatic cancer are also common causes of exocrine pancreatic insufficiency (EPI), which is characterized by inadequate pancreatic secretion of exocrine digestive enzymes. Although the association between EPI and pancreatic cancer has been thought to be linked by preceding chronic pancreatitis, it is unclear if EPI, regardless of etiology, is a risk factor or early marker for pancreatic cancer or cancer in general. Methods: This is a retrospective observational study utilizing the electronic health records of Ochsner Health System, Louisiana, over a 3-year period from January 2017 to January 2020 to identify patients with a diagnosis of EPI by ICD-10 codes. Two cohorts were reviewed: patients with EPI (n=677) and patients with pancreatitis (n=1852). Both history of acute and/or chronic pancreatitis were included in the pancreatitis cohort. The cohorts were compared based on cancer prevalence at the start and end of the 3 year observation period. Results: In the EPI cohort, the cancer prevalence was 15.95% (108) at start, and 43.9% (297) at end, (p<0.05); and pancreatic cancer prevalence at start was 6.65% (123) and 29.8% (552) at end (p<0.05). In the pancreatitis cohort, the cancer prevalence was 5.4% (100) at start and 15.9% (294) at end (p<0.05); and pancreatic cancer 0.8% at start and 5% at end (p<0.05). Conclusions: Over a 3 year period, the rise in prevalence of general cancer and pancreatic cancer was higher in the EPI cohort compared to the pancreatitis cohort. Additionally, there was a statistically significant 2.8-fold increase in prevalence of cancer diagnosis and 4.5-fold increase in prevalence of pancreatic cancer diagnosis in the EPI cohort over the 3 year observation period. Though this is an observational study, it suggests the possibility that EPI, regardless of etiology, may be an independent predictor/risk factor for the development of future cancer in general and pancreatic cancer in particular. In addition it appears that this risk potential is substantively greater than that from a history of pancreatitis alone.

Untargeted Analysis of Serum Metabolomes in Dogs with Exocrine Pancreatic Insufficiency.

Exocrine pancreatic insufficiency (EPI) is a malabsorptive syndrome resulting from insufficient secretion of pancreatic digestive enzymes. EPI is treated with pancreatic enzyme replacement therapy (PERT), but the persistence of clinical signs, especially diarrhea, is common after treatment. We used untargeted metabolomics of serum to identify metabolic disturbances associated with EPI and generate novel hypotheses related to its pathophysiology. Fasted serum samples were collected from dogs with EPI (n = 20) and healthy controls (n = 10), all receiving PERT. Serum metabolomes were generated using UPLC-MS/MS, and differences in relative metabolite abundances were compared between the groups. Of the 759 serum metabolites detected, 114 varied significantly (p < 0.05, q < 0.2) between dogs with EPI and healthy controls. Differences in amino acids (arginate, homoarginine, 2-oxoarginine, N-acetyl-cadaverine, and α-ketoglutaramate) and lipids (free fatty acids and docosahexaenoylcarnitine) were consistent with increased proteolysis and lipolysis, indicating a persistent catabolic state in dogs with EPI. Relative abundances of gut microbial metabolites (phenyllactate, 4-hydroxyphenylacetate, phenylacetyl-amino acids, catechol sulfates, and o-cresol-sulfate) were altered in dogs with EPI, consistent with disruptions in gut microbial communities. Increased kynurenine is consistent with the presence of intestinal inflammation in dogs with EPI. Whether these metabolic disturbances participate in the pathophysiology of EPI or contribute to the persistence of clinical signs after treatment is unknown, but they are targets for future investigations.

Effects of dietary soybean meal on the digestive physiology of red seabream Pagrus major

To clarify the effects of dietary soybean meal (SBM) on the digestive physiology of red seabream Pagrus major, two isonitrogenous and isolipidic diets; a fishmeal-based diet (diet FM) and a SBM-based diet (diet SBM), were prepared and the acute and chronic effects of the diets on the digestive physiology of the fish were examined. In the acute effects trial (<48 h), the only difference observed was a lower level of trypsin activity in the intestinal content of the SBM group than the FM group, indicating that SBM administration reduces trypsin secretion on a short-term basis. In the chronic effects trial (six weeks), there were clear differences in several parameters assessed. There was a clear retardation of growth in fish fed the SBM diet, in addition to a faster gastric transit rate, stacked intestinal content, lower gallbladder weight, lower activities/gene expression levels of hepatopancreatic enzymes (trypsin, chymotrypsin, amylase and/or lipase) and reduced protease activity (trypsin and chymotrypsin) in the intestinal content compared to fish fed the FM diet. Taken together, these results indicate that feeding SBM over a long period (chronic exposure) leads to reduced storage, production and secretion of bile and pancreatic digestive enzymes. SBM protein does not appear to fully activate or stimulate the digestive system of red seabream in either the short or long term. This may be due to a lack of stimulation or to an inhibitory effect that becomes more pronounced on a long-term basis. Such inhibition of the digestive process may be one of the main reasons for the low growth performance observed in fish fed SBM-based diets.

Yarrowia lipolytica Lipase 2 Is Stable and Highly Active in Test Meals and Increases Fat Absorption in an Animal Model of Pancreatic Exocrine Insufficiency

Pancreatic exocrine insufficiency (PEI) reduces pancreatic secretion of digestive enzymes, including lipases. Oral pancreatic enzyme replacement therapy (PERT) with pancreatin produces unsatisfactory results. The lipase 2 produced by the yeast Yarrowia lipolytica (YLLIP2; GenBank: AJ012632) might be used in PERT. We investigated its ability to digest triglycerides in a test meal and its efficacy in reducing fecal fat in an animal model of PEI. YLLIP2 was produced by genetically engineered Y lipolytica and purified from culture media. YLLIP2 or other gastric (LIPF) and pancreatic (PNLIPD) lipases were added to a meal paste containing dietary triglycerides, at a range of pH values (pH 2-7), with and without pepsin or human bile and incubated at 37°C. We collected samples at various time points and measured lipase activities and stabilities. To create an animal model of PEI, steatorrhea was induced by embolization of the exocrine pancreas gland and pancreatic duct ligation in minipigs. The animals were given YLLIP2 (1, 4, 8, 40, or 80 mg/d) or pancreatin (100,000 US Pharmacopeia lipase units/d, controls) for 9 days. We then collected stool samples, measured fat levels, and calculated coefficient of fat absorption (CFA) values. YLLIP2 was highly stable and poorly degraded by pepsin, and had the highest activity of all lipases tested on meal triglyceride at pH 4-7 (pH 6 with bile: 94 ± 34 U/mg; pH 4 without bile: 43 ± 13 U/mg). Only gastric lipase was active and stable at pH 3, whereas YLLIP2 was sensitive to pepsin hydrolysis after pH inactivation. From invitro test meal experiments, the lipase activity of YLLIP2 (10 mg) was estimated to be equivalent to that of pancreatin (1200 mg; 100,000 US Pharmacopeia units) at pH 6. In PEI minipigs, CFA values increased from 60.1% ± 9.3% before surgery to 90.5% ± 3.2% after administration of 1200 mg pancreatin (P < .05); CFA values increased to a range of 84.6% ± 3.0% to 90.0% ± 3.8% after administration of 4-80 mg YLLIP2 (P < .05). The yeast lipase YLLIP2 is stable and has high levels of activity against test meal triglycerides in a large pH range, with and without bile. Oral administration of milligram amounts of YLLIP2 significantly increased CFA values, similar to that of 1.2 g pancreatin, in a minipig model of PEI.

Effects of Alcohol Extract from Soybean Meal on Pancreatic Digestive Enzyme and Bile Acid Secretion in Yellowtail Seriola quinqueradiata

Effects of Alcohol Extract from Soybean Meal on Pancreatic Digestive Enzyme and Bile Acid Secretion in Yellowtail Seriola quinqueradiata

Digestive Enzyme Secretion, Intuition, and the History of Science: Part II

A companion paper explored the role of intuition in the genesis of an alternative theory for the secretion of pancreatic digestive enzymes, looking through the lens of three philosophers/historians of science. Gerald Holton, the last scholar, proposed that scientific imagination is shaped by a number of thematic presuppositions, which function largely below awareness. They come in pairs of opposites that alternately gain cultural preeminence. The current paper examines three thematic presuppositions inherent to both the generally accepted model for digestive enzyme secretion and most consciousness-centered views of higher-level cognition—discreteness, reduction, and simplicity. Since they often build on each other, together they are referred to as the simplicity worldview. Also considered are the three opposite thematic assumptions inherent to both the alternative model for digestive enzyme secretion and intuition-friendly views of higher-level cognition—the continuum, holism, and complexity—together referred to as the complexity worldview. The article highlights the potential importance to scientific knowledge of this currently less favored worldview.

Trusting Your Gut, Among Other Things: Digestive Enzyme Secretion, Intuition, and the History of Science

The role of intuition in scientific endeavor is examined through the lens of three philosophers/historians of science—Karl Popper, Thomas Kuhn, and Gerald Holton. All three attribute an important role to imagination/intuition in scientific endeavor. As a case study, the article examines the controversy between the generally accepted Vesicular Sequestration/Exocytosis Model of pancreatic digestive enzyme secretion and an alternative view called the Equilibrium Model. It highlights the intertwining of intuition and reason in the genesis of the Equilibrium Model developed in response to findings that could not readily be explained by the consensus view. It suggests that tacit knowledge/understanding works in conjunction with philosophical and aesthetic presuppositions that function to a greater or lesser extent below awareness. Together they guide judgments about whether falsification has occurred and help frame alternative theories.

Small G proteins as key regulators of pancreatic digestive enzyme secretion

Small GTP-binding (G) proteins act as molecular switches to regulate a number of cellular processes, including vesicular transport. Emerging evidence indicates that small G proteins regulate a number of steps in the secretion of pancreatic acinar cells. Diverse small G proteins have been localized at discrete compartments along the secretory pathway and particularly on the secretory granule. Rab3D, Rab27B, and Rap1 are present on the granule membrane and play a role in the steps leading up to exocytosis. Whether the function of these G proteins is simply to ensure appropriate targeting or if they are involved as regulatory molecules is discussed. Most evidence suggests that Rab3D and Rab27B play a role in tethering the secretory granule to its target membrane. Other Rabs have been identified on the secretory granule that are associated with different steps in the secretory pathway. The Rho family small G proteins RhoA and Rac1 also regulate secretion through remodeling of the actin cytoskeleton. Possible mechanisms for regulation of these G proteins and their effector molecules are considered.

Fat taste and lipid metabolism in humans

Dietary and body fat are essential for life. Fatty acids modulate fat detection, ingestion, digestion, absorption and elimination. Though direct effects occur throughout the body, much of this regulation stems from signals originating in the oral cavity. The predominant orosensory cue for dietary fat is textural, but accumulating electrophysiological, behavioral and clinical evidence supports olfactory and gustatory components. Orosensory stimulation with long-chain unsaturated, but possibly also saturated, fatty acids elicits an array of cephalic phase responses including release of gastric lipase, secretion of pancreatic digestive enzymes, mobilization of lipid stored in the intestine from the prior meal, pancreatic endocrine secretion and, probably indirectly, altered lipoprotein lipase activity. Combined, these processes influence postprandial lipemia. There is preliminary evidence of marked individual variability in fat “taste” with uncertain health implications. The possibility that fat taste sensitivity reflects systemic reactivity to fat warrants further evaluation.

Pancreatic Amylin as a Centrally Acting Satiating Hormone

This review summarizes the present knowledge concerning the anorectic action of the pancreatic hormone amylin. It focuses mainly on the role of amylin as a short term satiating peptide. Since there is some evidence however that basal amylin levels might play a role in the long term control of food intake and/or body weight, this aspect will be discussed briefly towards the end of this review. Concerning amylin as a satiating hormone, it is well established that amylin is released during meals, and that exogenous amylin leads to a dose-related reduction in meal size. Amylin has a rapid onset and brief duration of action. The area postrema (AP) plays a predominant role in peripheral amylin's satiating effect, involving a direct activation of AP neurons by blood-borne amylin. The nucleus of the solitary tract (NTS) relays this effect to higher brain structures, the lateral parabrachial nucleus, and possibly the central nucleus of the amygdala and the bed nucleus of the stria terminalis. Amylin's anorectic effect may in part be due to reduced expression of orexigenic neuropeptides in the lateral hypothalamic area. The anorectic action of amylin is one important factor in amylin's overall role to control the influx of nutrients into the circulation. By reducing food intake, gastric acid secretion, limiting the rate of gastric emptying and diminishing pancreatic glucagon and digestive enzyme secretion, amylin regulates nutrient appearance and postprandial glucose concentration. Amylin seems to be a necessary and complementary factor to insulin, which regulates the rate of nutrient disappearance. In this sense, amylin and insulin are adjunct players in the control of nutrient fluxes, and amylin's role to control feeding is a pivotal factor in this regard.

The role of the pancreatic renin–angiotensin system in acinar digestive enzyme secretion and in acute pancreatitis

The pancreas contains a local renin–angiotensin system (RAS), which is subject to activation by experimental pancreatitis. In the exocrine pancreas, angiotensin II receptor subtypes AT 1 and AT 2 have been localized in the pancreatic ducts, blood vessels and acinar cells. We hypothesize that local RAS activities may have a potential role in regulating pancreatic acinar digestive enzyme secretion. The present study was designed to elucidate firstly the existence of RAS components in pancreatic acinar cells and their regulation by acute pancreatitis. Secondly, the differential roles of AT 1 and AT 2 receptors in controlling digestive enzyme secretion from dispersed functional pancreatic acini were also investigated. The mRNA levels of RAS components were assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Acinar secretions were assayed by the measurement of α-amylase and lipase activities. Induction of acute pancreatitis was achieved by hyperstimulation of two intraperitoneal (i.p.) injections of cerulein (50 μg/kg/h). Results from RT-PCR showed that the mRNA levels of the major RAS components (angiotensinogen, AT 1 and AT 2 receptors) were expressed in isolated rat pancreatic acinar cells, and they were upregulated during pancreatitis. Exogenous addition of angiotensin II could stimulate a dose-dependent release of digestive enzymes from the acinar cells. Administration of the selective AT 1 receptor antagonist losartan significantly inhibited the acinar digestion enzyme secretion in both normal and pancreatitis-induced acini. However, a specific AT 2 receptor blocker PD123319 did not exhibit such a suppressive effect. These data indicate the existence of an acinar RAS in the pancreas of potential importance in the physiological regulation of digestive enzyme secretion. The differential actions of AT 1 and AT 2 receptors and their upregulation may have clinical relevance to the pathogenesis and management of acute pancreatitis.

Pathophysiology of alcohol-induced pancreatic injury.

The evidence that ethanol abuse can lead to pancreatitis is overwhelming, but the mechanism(s) by which ethanol causes pancreatic injury and pancreatitis are not known. Many studies have focused on short-term effects of ethanol administration on exocrine pancreatic function, but the results reported have been variable and no clear picture has emerged. Attempts to induce pancreatitis by long-term ethanol administration have, for the most part, failed. We evaluated the effects of ethanol administration on pancreatic secretion of digestive enzymes. These studies indicate that administration of ethanol results in a transient increase in pancreatic amylase output and plasma cholecystokinin (CCK) levels. This phenomenon is mediated by a trypsin-sensitive CCK-releasing factor that is present within the duodenal lumen. These observations lead us to speculate that repeated CCK-mediated, ethanol-induced stimulation of pancreatic digestive enzyme secretion may play a role in the events that link ethanol abuse to the development of pancreatic injury.

Secretion of pancreatic digestive enzymes induced in rats by first-time oral exposure to kidney bean E2L2 lectin is mediated only in part by cholecystokinin (CCK).

The acute effects of kidney bean (Phaseolus vulgaris) E2L2 lectins (PHA) given orally to conscious rats or continually infused into the duodenum of anesthetized rats on blood cholecystokinin (CCK), secretin, and gastrin and on secretion of pancreatic digestive enzymes have been evaluated. PHA increased circulating levels of CCK and secretin but did not alter gastrin. In addition, PHA induced dose-dependent secretion of trypsinogen, chymotrypsinogen, and alpha-amylase by the pancreas in vivo. This pancreas output appeared to be modulated only in part through CCK. Thus pretreatment of rats with a CCK-A receptor antagonist (L-364718) attenuated the immediate (< or = 90 min) pancreas secretory response to PHA but could not prevent a PHA-associated increase in digestive enzyme output in the longer term (after 90 min). In contrast, treatment of rats with L-364718 abolished the stimulatory effects of soyabean trypsin inhibitors on digestive enzyme secretion in both the short and long term. Additional mechanisms or hormones, such as secretin, may play a role in modulating later exocrine pancreas responses to PHA.

A cholecystokinin-releasing factor mediates ethanol-induced stimulation of rat pancreatic secretion.

The mechanisms by which short-term ethanol administration alters pancreatic exocrine function are unknown. We have evaluated the effects of ethanol administration on pancreatic secretion of digestive enzymes. In our studies, anesthetized as well as conscious rats were given ethanol at a rate sufficient to cause the blood ethanol concentration to reach levels associated with clinical intoxication. Ethanol was administered over a 2-h period during which blood ethanol levels remained stably elevated. We report that intravenous administration of ethanol results in a transient increase in pancreatic amylase output and plasma cholecystokinin (CCK) levels. The ethanol-induced increase in amylase output can be completely inhibited by the CCK-A receptor antagonist L-364,718 and partially inhibited by the muscarinic cholinergic antagonist atropine. The ethanol-induced rise in amylase output can be completely prevented by instillation of trypsin into the duodenum or by lavage of the duodenum with saline during ethanol administration. Furthermore, the intraduodenal activity of a CCK-releasing factor is increased by infusion of ethanol. These studies indicate that administration of ethanol causes rat pancreatic exocrine secretion to increase. This phenomenon is mediated by a trypsin-sensitive CCK-releasing factor which is present within the duodenal lumen. These observations lead us to speculate that repeated CCK-mediated ethanol-induced stimulation of pancreatic digestive enzyme secretion may play a role in the events which link ethanol abuse to the development of pancreatic injury.

Both free and complexed trypsin inhibitors stimulate pancreatic secretion and change duodenal enzyme levels.

Secretion of pancreatic digestive enzymes was measured in pancreatic cannulated rats after duodenal stimulation with Kunitz or Bowman-Birk protease inhibitors or their complexes with trypsin and/or chymotrypsin. Free and complexed inhibitors were bound by the duodenal epithelium, stimulated the discharge of cholecystokinin, and significantly increased secretion rates of alpha-amylase, trypsinogen, and chymotrypsinogen. Inasmuch as secretion rates returned to basal levels with cholecystokinin-A receptor antagonists, the stimulation was likely to be mediated by cholecystokinin. Soya factors also influenced the duodenal concentration of pancreatic enzymes under simulated feeding conditions. Thus the level of alpha-amylase increased while the trypsin concentration decreased in rats gavaged with free or complexed inhibitors. The same was true for chymotrypsin when the Bowman-Birk inhibitor was used, but the Kunitz inhibitor and its trypsin complex actually raised the luminal concentration of chymotrypsin. Accordingly, because soya inhibitors remained effective in stimulating pancreatic secretion after elimination of their inhibitory activity by complex formation, it is questionable whether the signal for cholecystokinin secretion was solely due to lowering of duodenal protease levels.

Modulation of pancreatic secretion of individual digestive enzymes in octreotide (SMS 201-995)-infused rats.

We demonstrated previously that pancreatic secretion of individual enzymes is specifically regulated (1). In the present study, we investigated and defined contributing roles of cholinergic and cholecystokinin tones to the specific regulation of rat pancreatic secretion of digestive enzymes. Animals were provided with pancreatic, biliary, duodenal, and jugular vein cannulas allowing separate drainage of bile and pure pancreatic juice, as well as intravenous infusions of MK329 or atropine sulfate along with SMS 201-995 (SMS). Rats kept in restraint cages were divided into four groups. The first rat group was infused with 5 micrograms kg-1 h-1 SMS alone; the second group was infused with a mixture of SMS and MK329 (5 micrograms kg-1 h-1:0.5 mg kg-1 h-1); the third group received a mixture of SMS and atropine (5 micrograms kg-1 h-1); and rats in the fourth group were administrated a mixture of SMS, MK329, and atropine (5 micrograms kg-1 h-1:0.5 mg kg-1:100 micrograms kg-1 h-1). Food, but not water, was denied rats 10 h before the experiment and throughout the 6-h experimental period. During the experiment, pancreatic juice was continuously collected every 15 min from each rat, and a 15-microliter aliquot of the pancreatic juice sample was removed for total protein, amylase, lipase, trypsinogen, chymotrypsinogen, and proelastase assays. Pancreatic juice previously collected from a donor rat was mixed with the fresh bile and the mixture was recirculated into the duodenum. The secretory patterns over the 6-h experimental period showed that during the first hour of drug infusion, MK329 alone did not alter the SMS-induced inhibitory process of total protein and amylase, trypsinogen, and proelastase secretion, and there was no marked change in total protein and enzyme outputs. Adding atropine to SMS did not alter the secretory pattern during the first hour of drug infusion, but a significantly greater decrease in protein and enzymes outputs occurred. Correlations between paired enzyme outputs greatly increased with SMS alone, but some changed when either MK329 or atropine was infused along with SMS. When all drugs were infused together, enzyme outputs became strongly correlated. These results suggest that under fasting conditions, somatostatin and atropine can neutralize basal pancreatic enzyme outputs, leading to a constitutive type of secretion characterized by parallel secretion of the digestive enzymes. Furthermore, it is proposed that under basal secretion conditions, acetylcholine and cholecystokinin reaching the pancreatic acinar cells may act to dissociate pancreatic secretion of individual digestive enzymes originating from heterogeneous secretory granules.

Stimulus-secretion coupling of pancreatic digestive enzyme secretion.

Stimulus-secretion coupling of pancreatic digestive enzyme secretion.

Amylin mobilizes [Ca2+]i and stimulates the release of pancreatic digestive enzymes from rat acinar AR42J cells: evidence for an exclusive receptor system of amylin.

Amylin dose-dependently stimulated the secretion of amylase and cholesterol esterase from rat pancreatic acinar AR42J cells. The biochemical basis of this action was investigated using fura-2-loaded AR42J cells. Amylin increased intracellular free calcium. [Ca2+]i, in a dose-dependent manner. The Ca2+ signal persisted even in Ca(2+)-free medium, suggesting mobilization from intracellular stores rather than influx. Consistently, thapsigargin abolished amylin-induced responses, suggesting that Ca2+ is released from an inositol 1,4,5-triphosphate (IP3)-sensitive pool. This was confirmed by the finding that amylin elevated IP3 levels. AR42J cells pretreated with amylin did not respond to amylin, suggesting that the receptors mediating this response undergo homologous desensitization. However, pretreatment with related peptides, calcitonin gene-related peptide (CGRP) and salmon calcitonin, did not diminish [Ca2+]i mobilization by amylin. CGRP and calcitonin also failed to mobilize [Ca2+]i even at 10 microM. These results suggests that the stimulatory effects of amylin on pancreatic digestive enzyme secretion from AR42J cells are mediated by a G-protein-linked membrane receptor coupled to IP3-dependent calcium pools.

Stability of circadian and minor cycles of exocrine pancreatic secretion in atropine- and MK-329-infused rats.

We previously demonstrated the existence of a circadian rhythm of pancreatic secretion of fluid and digestive enzymes, which was superimposed on by a regular 1.84-h minor cycle of exocrine pancreatic secretion of fluid and total protein, amylase, and chymotrypsinogen (25). Direct control of these daily and hourly rhythms of pancreatic secretory function has not been addressed. Cholinergic and cholecystokinin (CCK)-associated influences on these two rhythms of exocrine pancreatic secretion were investigated in rats provided with pancreatic, biliary, duodenal, and jugular vein cannulas, allowing separate drainage of bile and pure pancreatic juice, as well as intravenous infusions of atropine sulfate and/or MK-329. Rats were kept in restraint cages under controlled temperature and humidity, with a regular 12-h light cycle, and divided into five groups. The first group of fed rats was constantly infused with 200 micrograms.kg-1.h-1 atropine, the second with 0.5 mg.kg-1.h-1 MK-329, and the third with both. In the group where both drugs were simultaneously infused, 500 micrograms.kg-1.h-1 atropine was intraperitoneally administered, whereas MK-329 was infused by intravenous cannula. Two groups consisted of fasted rats, of which one was also given atropine (100 micrograms.kg-1.h-1). Three-day experiments were performed separately with fed rats, and 2-day experiments were performed with fasted rats; atropine and/or MK-329 infusion, starting on day 2, was constant over 48 h in both fed and fasted rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Pancreatic protease secretion profiles after spontaneous feeding of casein or soybean protein diet in unrestrained conscious rats

Under unrestrained physiologic conditions, the exocrine pancreatic secretion of digestive enzymes were observed with chronic bile-pancreatic duct cannulated rats. Bile-pancreatic juice (BPJ) was intermittently collected after spontaneous feeding of an 8% casein or an 8% soybean protein isolate (SPI) diet under recirculation of BPJ to the duodenum. The operative damage of cannula implantation was recovered for 5 days on a 25% casein diet, which was examined by food consumption and the basal secretion (pancreatic secretion during fasting) of total protein and trypsin. After feeding of both the test diets, the secretions of total protein, trypsin, chymotrypsin, and carboxypeptidase A were increased rapidly and about two-fold from the basal secretion. There were peak values at 15 min in the SPI group and at 30 min in the casein group. In the casein-fed rats, the protein and protease secretions maintained high levels for the initial 150 min, but in the SPI fed rats those secretions were decreased from 15 min after feeding. The protein and protease secretions tended to be higher in the casein group than in the SPI group after 30 min, and effect of ‘diet’ was significant in analysis of variance. The secretion profiles of protein and three proteases were similar, and specific activities of three proteases were not increased significantly in both the groups. We conclude that these low-protein diets are potent stimulators of the exocrine pancreatic secretion after spontaneous feeding in unrestrained rats.