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1.
The effects of various amino acids and phosphorylated forms of glucose on the release of digestive enzymes from particulate cellular pools, particularly zymogen granules, were evaluated in rat pancreas. Whole tissue homogenates, as well as zymogen granules isolated either by differential centrifugation in 0.3 M sucrose or by preparation in buffered sucrose and subsequent centrifugation in a Percoll gradient, were studied. The basic amino acids L-arginine and L-lysine, sites of tryptic cleavage, caused the release of trypsinogen, but not chymotrypsinogen, whereas the aromatic amino acids L-phenylalanine and L-tryptophan, sites of chymotryptic cleavage, caused release of both trypsinogen and chymotrypsinogen. Neither led to the release of the starch-splitting enzyme amylase. All effects occurred within the range of normal plasma concentrations for these amino acids in the rat. Two amino acids, L-threonine and hydroxy-L-proline, that are not sites of cleavage by trypsin or chymotrypsin, and a nonmammalian amino acid, aminoadipic acid, did not lead to release of trypsinogen, chymotrypsinogen, or amylase. Two phosphorylated forms of glucose, glucose 1-phosphate and glucose 1,6-diphosphate, caused the release of amylase, but of neither trypsinogen nor chymotrypsinogen. Contrary to previous results, D-glucose was without effect, as was glucose 6-phosphate. We propose that certain digestive end products, by direct action on zymogen granules, cause the selective release of the enzymes involved in their evolution from polymeric substrates during digestion. 相似文献
2.
A P Majumdar M A Dubick G D Vesenka H T Billy M C Geokas 《Biochemical and biophysical research communications》1985,128(2):872-877
The secretion of amylase, trypsinogen, chymotrypsinogen and proelastase from isolated rat dispersed pancreatic acini was investigated in the absence (basal) and presence of two concentrations of CCK8 (50 and 500 pM), carbachol (2.5 and 7.5 microM) and secretin (10 nM and 1 microM). The unstimulated (basal) rate of release of each of the digestive enzymes was essentially the same. However, whereas both doses of CCK8 and carbachol caused a preferential release of chymotrypsinogen over that of amylase and trypsinogen, the magnitude of stimulated release of amylase, trypsinogen and chymotrypsinogen by 1 microM secretin was found to be similar for each of the enzymes. Furthermore, none of the secretagogues caused a significant enhancement in proelastase release. The present data demonstrate that whereas CCK8 and carbachol induce a greater release of chymotrypsinogen over that of amylase or trypsinogen, release of all three enzymes was equally stimulated by secretin from isolated pancreatic acini. 相似文献
3.
S I Yang M Furuse T Muramatsu J Okumura 《Comparative biochemistry and physiology. A, Comparative physiology》1989,93(4):703-706
1. Effect of amino acid administration on pancreatic secretion of digestive enzymes, amylase, trypsinogen and chymotrypsinogen was studied after wing vein injection of an amino acid (AAs) mixture (Thr, Lys, Phe, Leu, Ile, Glu, Val, His, and Met) or combinations of selected amino acids, i.e. Thr + Phe + Ile, Thr + Phe, Thr + Ile or Phe + Ile, in the presence of cholecystokinin (CCK) in chicks. 2. Time course changes of enzyme output were similar in all treatment groups having a peak within 10-30 min, except for Phe + Ile that resulted in delayed induction of the enzyme release as shown by significant increases in the last 20 min compared with those in the rest. 3. When increases in enzyme outputs for the first 30 min were compared, it was shown that the three enzyme responses brought about by the administration of the AAs mixture was almost entirely accounted for by the combined injection of Thr + Phe. 4. Neither Thr + Ile nor Phe + Ile was as effective as Thr + Phe in inducing the output of these pancreatic enzymes. 5. The present results suggest that Thr and Phe may have a specific regulatory role in the secretion of pancreatic digestive enzymes in chicks when administered simultaneously. 相似文献
4.
Effect of exogenous and endogenous insulin on the secretory response of the pancreas to the octapeptide of cholecystokinin (CCK8) in normal rats 总被引:1,自引:0,他引:1
A Sofranková 《Physiologia Bohemoslovaca》1984,33(5):391-398
The author studied the effect of insulin on CCK8-stimulated secretion by the pancreas. CCK8 (0.6 nmol.kg-1) was administered to normal anaesthetized rats 30 min after the intravenous injection of insulin (10 U.kg-1), glucose (2 g.kg-1) or NaCl (controls). Pancreatic juice was collected from the intubated common bile duct. In rats given exogenous insulin, there were no statistically significant differences in total protein, amylase and trypsinogen output after CCK8 compared with the controls. In rats in which endogenous insulin secretion was stimulated with glucose, the amylase response to CCK8 was not significantly different from the control animals, but the trypsinogen response was significantly lower. The results show that insulin, in some still unknown manner, inhibits the trypsinogen secretory response to CCK8. In addition, they confirm data claiming that the synthesis and secretion of pancreatic amylase require a given critical ratio of insulin to glucose, or of insulin to the factor stimulating pancreatic secretion. 相似文献
5.
We have attempted to demonstrate a pancreatic secretory response to intraduodenal amino acids in the anesthetized cat. In four cats stimulated with supramaximal doses of secretin, protein concentrations in pancreatic juice were measured after intraduodenal bolus injection of various amino acids, IV CCK, or electrical stimulation of the vagus nerve. In addition, the duodenum was perfused with phenylalanine (50 mM) for 30 min in two cats, and the vagus nerve stimulated electrically for 15 min in one. In no case did amino acids produce pancreatic protein secretion, whereas CCK and vagal stimulation always did so. We conclude that this insensitivity to amino acids in the cat is a species difference from the dog and man. 相似文献
6.
Murashita K Fukada H Rønnestad I Kurokawa T Masumoto T 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2008,150(4):438-443
Cholecystokinin (CCK) and neuropeptide Y (NPY)-related peptides are key regulators of pancreatic enzyme secretion in vertebrates. CCK stimulates enzyme secretion whereas peptide Y (PY), a NPY-related peptide, plays an antagonistic role to that of CCK. In fish, very little is known about how different nutrients affect the synthesis of CCK and PY in the digestive tract, and the mechanism by which CCK and PY actually regulate digestive enzyme secretion is not well understood. In order to determine how different nutrients stimulate the synthesis of CCK and PY in yellowtail (Seriola quinqueradiata), CCK and PY mRNA levels in the digestive tract were measured after oral administration of a single bolus of either phosphate-buffered saline (PBS: control), starch (carbohydrate), casein (protein), oleic acid (fatty acid) or tri-olein (triglyceride). In addition, in order to confirm the synthesis and secretion of digestive enzymes, the mRNA levels and enzymatic activities of three digestive enzymes (lipase, trypsin and amylase) were also analyzed. Casein, oleic acid and tri-olein increased the synthesis of lipase, trypsin and amylase, while starch and PBS did not affect the activity of any of these enzymes. CCK mRNA levels rose, while PY mRNA levels were reduced in fish administered casein, oleic acid and tri-olein. These results suggest that in yellowtail, CCK and PY maintain antagonistic control of pancreatic enzyme secretion after intake of protein and/or fat. 相似文献
7.
Oral application of a single dose of a new synthetic proteinase inhibitor Camostate (Foy-305) in male Wistar rats was carried out together with studies of in vitro amino acid incorporation followed by separation of proteins by two-dimensional gel electrophoresis. The aim of this experiment was to analyze changes produced by the inhibitor in total protein and individual enzyme biosynthesis. Administration of 100 mg/kg Foy-305 resulted in significant inhibition of total pancreatic protein synthesis, without changes in fractional rates for individual enzymes. 50 mg/kg Foy-305 induced a 10-fold elevation of cholecystokinin (CCK) levels in serum; this persisted for 3 h and led to a significant increase in the total rate of protein synthesis with peak values at 6 and 9 h (78% and 84% above control levels, respectively), returning to control by 15 h. Changes in fractional rates of synthesis occurred with a latency of 6 h and were restricted to amylase and the anionic form of trypsinogen and chymotrypsinogen. Amylase biosynthesis decreased by about 40% from control levels at 9 h to return to control levels by 15 h. Increased synthesis of trypsinogen and chymotrypsinogen was observed; this was also phasic. The results show similar enzyme-specific regulation as previously described for exogenous CCK stimulation and for the adaptation of the pancreas to diets enriched in protein. They demonstrate the effectiveness of pulsatory endogenous hormone release in the regulation of protein synthesis. 相似文献
8.
Cammisotto PG Gélinas Y Deshaies Y Bukowiecki LJ 《American journal of physiology. Endocrinology and metabolism》2005,289(1):E166-E171
The aim of the present study was to determine the respective roles of energy substrates and insulin on leptin secretion from white adipocytes. Cells secreted leptin in the absence of glucose or other substrates, and addition of glucose (5 mM) increased this secretion. Insulin doubled leptin secretion in the presence of glucose (5 mM), but not in its absence. High concentrations of glucose (up to 25 mM) did not significantly enhance leptin secretion over that elicited by 5 mM glucose. Similar results were obtained when glucose was replaced by pyruvate or fructose (both 5 mM). L-Glycine or L-alanine mimicked the effect of glucose on basal leptin secretion but completely prevented stimulation by insulin. On the other hand, insulin stimulated leptin secretion when glucose was replaced by L-aspartate, L-valine, L-methionine, or L-phenylalanine, but not by L-leucine (all 5 mM). Interestingly, these five amino acids potently increased basal and insulin-stimulated leptin secretion in the presence of glucose. Unexpectedly, L-glutamate acutely stimulated leptin secretion in the absence of glucose or insulin. Finally, nonmetabolizable analogs of glucose or amino acids were without effects on leptin secretion. These results suggest that 1) energy substrates are necessary to maintain basal leptin secretion constant, 2) high availability of glycolysis substrates is not sufficient to enhance leptin secretion but is necessary for its stimulation by insulin, 3) amino acid precursors of tricarboxylic acid cycle intermediates potently stimulate basal leptin secretion per se, with insulin having an additive effect, and 4) substrates need to be metabolized to increase leptin secretion. 相似文献
9.
Considerable controversy has surrounded the question of whether the exocrine pancreas discharges digestive enzymes in a parallel or nonparallel fashion. A recent report (Rothman, S.S., and Wilking, H. (1978) J. Biol. Chem. 253, 3543-3549) claimed that the in vitro rabbit pancreas demonstrated nonparallel enzyme discharge after stimulation with cholecystokinin/pancreozymin, but that parallel discharge followed stimulation with the COOH-terminal octapeptide of cholecystokinin/pancreozymin. It was suggested that the full hormone acted to inhibit chymotrypsinogen secretion while stimulating trypsinogen secretion. Because of the fundamental importance of this question to our understanding of the exocrine secretion of exportable proteins, we have repeated these experiments using the same preparation and stimulant but have observed only parallel enzyme discharge. We conclude that it is unlikely that cholecystokinin/pancreozymin causes the selective inhibition of chymotrypsinogen secretion. 相似文献
10.
Effects of dexamethasone and 5-bromodeoxyuridine on protein synthesis and secretion during in vitro pancreatic development 总被引:1,自引:0,他引:1
Protein synthesis and secretion during in vitro pancreatic development and after treatment with the glucocorticoid dexamethasone and the thymidine analog 5-bromodeoxyuridine (BrdU) was monitored using two-dimensional gel electrophoresis. At 14 days gestation, the synthesis of more than 200 proteins and the secretion of a complex set of proteins was detected. The relative rate of synthesis and secretion of the majority of this set of proteins decreased dramatically during development; after 6 days of culture most were no longer detected. In contrast, the synthesis and secretion of pancreas-specific exocrine proteins amylase, a Sepharose binding protein (protein 2), and chymotrypsinogen first detected after one day in culture, increased throughout the 6-day culture period. Other pancreatic digestive (pro)enzymes normally found in the adult such as the basic form of chymotrypsinogen, lipase, ribonuclease, and trypsinogen were not detected during the culture period. Thus at least two distinct regulatory events are involved in the expression of the exocrine genes during development. Dexamethasone treatment during the 6-day culture period selectively increased the synthesis of amylase and several other minor secretory proteins. BrdU treatment caused major changes in the protein synthetic and secretory patterns of the pancreas as well as in morphogenesis. BrdU treated pancreases showed greatly reduced synthesis of amylase, protein 2, and chymotrypsinogen and prolonged synthesis of many proteins normally detected only at early stages of pancreatic development. BrdU treatment also stimulated the secretion of a set of proteins ostensibly associated with duct cells. Thus, BrdU specifically alters the developmental program of the pancreas. 相似文献
11.
The insulin response of 3-day old neonatal rat islets was evaluated following a 1 h incubation with glucose alone and in the presence of 30 nM sulfated cholecystokinin octapeptide (CCK) and/or 20 microM carbachol (CCh). Insulin secretion was found to be incrementally increased from the lowest glucose concentration and enhanced several fold in the presence of CCK and/or CCh. In combination, CCK and CCh increased glucose-stimulated insulin secretion by an amount equivalent to the sum of their individual increases. The presence of either CCK alone or CCK plus CCh increased phosphoinositide hydrolysis by the same relative amount that they increased insulin secretion when compared to 8.3 mM glucose. Glucose-stimulated insulin secretion was totally inhibited when calcium was omitted from the incubation buffer; this effect was partially negated by CCK alone and more so by CCK combined with CCh. Insulin secretion in response to 8.3 mM glucose alone was unchanged when calcium in the incubation buffer was increased from 1 to 5 mM; however, the insulin response to 16.7 mM glucose alone and 8.3 mM glucose in the presence of CCK and/or CCh was increased under this condition. Thus, we have shown that, even at 3 days postpartum, insulin secretion from isolated islets is a complex response capable of being molded by several secretagogues at once and ultimately determined by interplay of different signaling systems activated. 相似文献
12.
In rat pancreatic islets the effects of cholecystokinin-8 (CCK8) on glucose-mediated insulin release, 45Ca2+ net uptake, 45Ca2+ efflux, 86Rb+ efflux, cAMP- and cGMP levels were studied. In the presence of a substimulatory glucose concentration (3 mM) CCK8 concentrations of up to 1 microM had no effect on insulin release, but CCK8 at 10 nM potentiated the stimulatory effect of glucose (11.1 mM). 10 nM CCK8 enhanced glucose-stimulated 45Ca2+ net uptake but was ineffective at substimulatory glucose levels. CCK8 had no effect on cAMP and cGMP levels in the presence of 11.1 mM glucose, CCK8 increased 86Rb+ (a measure of K+) in the presence of both 3 and 11.1 mM glucose. This effect was abolished when Ca2+ was omitted from the perifusion medium. CCK8 did not alter glucose (11.1 mM)-stimulated 45Ca2+ efflux rate. These data indicate that (1) CCK8 potentiates glucose-stimulated insulin secretion possibly via an effect on Ca2+ uptake, 2) by affecting Ca2+ uptake, CCK8 enhances K+ efflux, and 3) CCK8 does not mediate its effect via cAMP or cGMP. With respect to 86Rb+ efflux the mechanism of CCK8 action appears to be different from that of glucose. When the mechanism of CCK action on islets is compared with that on exocrine pancreas (data from others) there are similarities (importance of Ca2+ uptake and non-importance of cAMP and cGMP). 相似文献
13.
Thrower EC Diaz de Villalvilla AP Kolodecik TR Gorelick FS 《American journal of physiology. Gastrointestinal and liver physiology》2006,290(5):G894-G902
Pathological activation of digestive zymogens within the pancreatic acinar cell initiates acute pancreatitis. Cytosolic events regulate this activation within intracellular compartments of unclear identity. In an in vivo model of acute pancreatitis, zymogen activation was detected in both zymogen granule-enriched and microsomal cellular fractions. To examine the mechanism of this activation in vitro, a reconstituted system was developed using pancreatic cytosol, a zymogen granule-enriched fraction, and a microsomal fraction. Addition of cytosol to either particulate fraction resulted in a prominent increase in both trypsin and chymotrypsin activities. The percentage of the pool of trypsinogen and chymotrypsinogen activated was about twofold and sixfold greater, respectively, in the microsomal than in the zymogen granule-enriched fraction. Activation of chymotrypsinogen but not trypsinogen was significantly enhanced by ATP (5 mM) but not by the inactive ATP analog AMP-PNP. The processing of procarboxypeptidase B to its mature form also demonstrated a requirement for ATP and cytosol. E64d, an inhibitor of cathepsin B, a thiol protease that can activate trypsin, completely inhibited trypsin activity but did not affect chymotrypsin activity or carboxypeptidase B generation. These studies demonstrate that both zymogen granule-enriched and microsomal fractions from the pancreas can support cytosol-dependent zymogen activation. A component of the activation of some zymogens, such as chymotrypsinogen and procarboxypeptidase, may depend on ATP but not on trypsin or cathepsin B. 相似文献
14.
Changes in content and secretion of pancreatic enzymes in the obese Zucker rat. 总被引:2,自引:2,他引:0
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The contents of three major digestive enzymes (amylase, lipase and chymotrypsinogen) were measured in the obese Zucker rat. Only minimal changes were found in 7-week-old rats, but in adult obese rats (14-16 weeks) the amylase content was decreased by 50%, whereas the lipase and chymotrypsinogen contents were increased by 45% and 20%, respectively, compared with lean controls. Abnormalities of enzyme secretion were also found. Since the changes observed in enzyme proportions in adult obese Zucker rats are qualitatively similar to those observed in insulinopenic diabetes and other states associated with decreased glucose metabolism, it is speculated that the abnormalities found in the obese Zucker rat may be due to decreased glucose metabolism in the exocrine tissue consequent to insulin resistance. 相似文献
15.
When porcine alpha-amylase or bovine chymotrypsinogen A was added to the medium bathing the rabbit pancreas in short-term organ culture, the secretion of these enzymes collected via the duct system increased greatly. To determine if it was indeed the amylase added to the bath that was recovered in secretion, endogenous enzyme stores were prelabeled during a 4 h incubation with [3H]-leucine and the specific radioactivity of amylase in secretion followed. The addition of unlabeled exogenous amylase to the bathing medium reduced the specific radioactivity of secreted amylase by about 90% suggesting that the response was due to the transpancreatic transport of the added enzyme. This inhibition was maintained over time, and was a result, not only of the increased secretion of unlabeled enzyme, but also of a 72% steady-state inhibition in the secretion of endogenous (labeled) amylase. This latter observation indicates that the exogenous enzyme crosses the acinar cell and mixes with endogenous cellular stores. A cellular route is also suggested by the observation that the addition of amylase to the bath increased the amylase concentration in ductal fluid relative to that in the bath by about 20 times; it did not reduce it as would be expected if paracellular shunts were involved. In addition, a cellular pathway is suggested by the observation that a 2 h prior incubation in bovine chymotrypsinogen resulted in a greatly augmented chymotrypsinogen response to a maximal cholinergic stimulus. In all, the data support the prediction of the equilibrium theory of digestive enzyme secretion that enzyme secretion should be responsive to mass action, and the prediction of the enteropancreatic circulation hypothesis that a capacity exists for a substantial transpancreatic flux of digestive enzyme. 相似文献
16.
Liou AP Sei Y Zhao X Feng J Lu X Thomas C Pechhold S Raybould HE Wank SA 《American journal of physiology. Gastrointestinal and liver physiology》2011,300(4):G538-G546
The extracellular calcium-sensing receptor (CaSR) has recently been recognized as an L-amino acid sensor and has been implicated in mediating cholecystokinin (CCK) secretion in response to aromatic amino acids. We investigated whether direct detection of L-phenylalanine (L-Phe) by CaSR results in CCK secretion in the native I cell. Fluorescence-activated cell sorting of duodenal I cells from CCK-enhanced green fluorescent protein (eGFP) transgenic mice demonstrated CaSR gene expression. Immunostaining of fixed and fresh duodenal tissue sections confirmed CaSR protein expression. Intracellular calcium fluxes were CaSR dependent, stereoselective for L-Phe over D-Phe, and responsive to type II calcimimetic cinacalcet in CCK-eGFP cells. Additionally, CCK secretion by an isolated I cell population was increased by 30 and 62% in response to L-Phe in the presence of physiological (1.26 mM) and superphysiological (2.5 mM) extracellular calcium concentrations, respectively. While the deletion of CaSR from CCK-eGFP cells did not affect basal CCK secretion, the effect of L-Phe or cinacalcet on intracellular calcium flux was lost. In fact, both secretagogues, as well as superphysiological Ca(2+), evoked an unexpected 20-30% decrease in CCK secretion compared with basal secretion in CaSR(-/-) CCK-eGFP cells. CCK secretion in response to KCl or tryptone was unaffected by the absence of CaSR. The present data suggest that CaSR is required for hormone secretion in the specific response to L-Phe by the native I cell, and that a receptor-mediated mechanism may inhibit hormone secretion in the absence of a fully functional CaSR. 相似文献
17.
Immunoreactive cholecystokinin (CCK) levels in human and rat plasma are described using a radioimmunoassay specific for the biologically active sulfated end of CCK. This assay detected significant changes in plasma cholecystokinin levels during intrajejunal administration of amino acids and intravenous infusions of CCK-8 which were followed by increased pancreatic secretion. In humans, the concentration (pg/ml) of plasma cholecystokinin increased from 10.8 to 18.9 following intrajejunal amino acid instillation and from 15.4 to 31.1 during CCK infusion, while pancreatic trypsin secretion increased more than 15 fold. Ingestion of a test meal also caused a rapid and significant elevation (P less than 0.05) in both plasma CCK (14.5-21.7 pg/ml) and gastrin (50-160 pg/ml) levels. In the rat, an injection of 46 ng of CCK-8 produced a 300% increase in immunoreactive plasma CCK levels (2 min) and caused peak pancreatic protein secretion within 5 min; 4 fold lower doses (11.5 ng) elevated plasma CCK by 38% and pancreatic protein secretion to a small but significant extent. The ability of this assay to detect various forms of sulfated CCK in human plasma was also determined. Following gel chromatography on Sephadex G-50, at least three different immunoreactive peaks were found in plasma from fasted subjects and after intrajejunal amino acid stimulation. While the lower molecular weight CCK peptides (CCK-8 and CCK-12) were detected in plasma from both fasted and stimulated subjects, the larger form (CCK-33) was only present in measurable concentrations after amino acid infusion. The simultaneous measurement of increased plasma CCK levels and pancreatic secretion and the changes in the distribution of CCK peptides following amino acid infusion provides strong support that this assay detects physiologically relevant changes in biologically active CCK peptides. 相似文献
18.
Chaudhuri A Husain SZ Kolodecik TR Grant WM Gorelick FS 《American journal of physiology. Gastrointestinal and liver physiology》2007,292(5):G1403-G1410
The pancreatic acinar cell has several phenotypic responses to cAMP agonists. At physiological concentrations of the muscarinic agonist carbachol (1 microM) or the CCK analog caerulein (100 pM), ligands that increase cytosolic Ca(2+), cAMP acts synergistically to enhance secretion. Supraphysiological concentrations of carbachol (1 mM) or caerulein (100 nM) suppress secretion and cause intracellular zymogen activation; cAMP enhances both zymogen activation and reverses the suppression of secretion. In addition to stimulating cAMP-dependent protein kinase (PKA), recent studies using cAMP analogs that lack a PKA response have shown that cAMP can also act through the cAMP-binding protein, Epac (exchange protein directly activated by cyclic AMP). The roles of PKA and Epac in cAMP responses were examined in isolated pancreatic acini. The activation of both cAMP-dependent pathways or the selective activation of Epac was found to enhance amylase secretion induced by physiological and supraphysiological concentrations of the muscarinic agonist carbachol. Similarly, activation of both PKA or the specific activation of Epac enhanced carbachol-induced activation of trypsinogen and chymotrypsinogen. Disorganization of the apical actin cytoskeleton has been linked to the decreased secretion observed with supraphysiological concentrations of carbachol and caerulein. Although stimulation of PKA and Epac or Epac alone could largely overcome the decreased secretion observed with either supraphysiological carbachol or caerulein, stimulation of cAMP pathways did not reduce the disorganization of the apical cytoskeleton. These studies demonstrate that PKA and Epac pathways are coupled to both secretion and zymogen activation in the pancreatic acinar cell. 相似文献
19.
O'Keefe SJ Lee RB Anderson FP Gennings C Abou-Assi S Clore J Heuman D Chey W 《American journal of physiology. Gastrointestinal and liver physiology》2003,284(1):G27-G36
In the nutritional management of digestive disorders, it is important to know the relative secretory and metabolic responses to enteral and parenteral feeding. Twenty-seven healthy volunteers were studied while receiving either oral drinks or duodenal infusions of a complex formula diet, duodenal or intravenous infusions of elemental (protein as free amino acids, low fat) formulae, or saline. Pancreaticobiliary secretory responses were measured by nasoduodenal polyethylene glycol perfusion and aspiration, while monitoring blood hormone and nutrient levels. Diets were matched for protein (1.5 g x kg(-1) x d(-1)) and energy (40 kcal x kg(-1) x d(-1)). Compared with placebo, all oroenteral diets stimulated amylase, lipase, trypsin, and bile acid secretion and increased plasma concentrations of gastrin and cholecystokinin, whereas intravenous feeding did not. The complex formula produced a similar response whether given as drinks or duodenal infusions. Changing the duodenal formula to elemental reduced enzyme secretion by 50%, independently of CCK. Higher increases in plasma insulin, glucose, and amino acids were noted with intravenous feeding. Delivering food directly to the intestine by a feeding tube does not reduce pancreaticobiliary secretion. Enteral "elemental" formulae diminish, but only intravenous feeding avoids pancreatic stimulation. Intravenous administration impairs metabolic clearance. 相似文献
20.
Wang Y Chandra R Samsa LA Gooch B Fee BE Cook JM Vigna SR Grant AO Liddle RA 《American journal of physiology. Gastrointestinal and liver physiology》2011,300(4):G528-G537
Cholecystokinin (CCK) is produced by discrete endocrine cells in the proximal small intestine and is released following the ingestion of food. CCK is the primary hormone responsible for gallbladder contraction and has potent effects on pancreatic secretion, gastric emptying, and satiety. In addition to fats, digested proteins and aromatic amino acids are major stimulants of CCK release. However, the cellular mechanism by which amino acids affect CCK secretion is unknown. The Ca(2+)-sensing receptor (CaSR) that was originally identified on parathyroid cells is not only sensitive to extracellular Ca(2+) but is activated by extracellular aromatic amino acids. It has been postulated that this receptor may be involved in gastrointestinal hormone secretion. Using transgenic mice expressing a CCK promoter driven/enhanced green fluorescent protein (GFP) transgene, we have been able to identify and purify viable intestinal CCK cells. Intestinal mucosal CCK cells were enriched >200-fold by fluorescence-activated cell sorting. These cells were then used for real-time PCR identification of CaSR. Immunohistochemical staining with an antibody specific for CaSR confirmed colocalization of CaSR to CCK cells. In isolated CCK cells loaded with a Ca(2+)-sensitive dye, the amino acids phenylalanine and tryptophan, but not nonaromatic amino acids, caused an increase in intracellular Ca(2+) ([Ca(2+)](i)). The increase in [Ca(2+)](i) was blocked by the CaSR inhibitor Calhex 231. Phenylalanine and tryptophan stimulated CCK release from intestinal CCK cells, and this stimulation was also blocked by CaSR inhibition. Electrophysiological recordings from isolated CCK-GFP cells revealed these cells to possess a predominant outwardly rectifying potassium current. Administration of phenylalanine inhibited basal K(+) channel activity and caused CCK cell depolarization, consistent with changes necessary for hormone secretion. These findings indicate that amino acids have a direct effect on CCK cells to stimulate CCK release by activating CaSR and suggest that CaSR is the physiological mechanism through which amino acids regulate CCK secretion. 相似文献