Infusion Of Secretin Research Articles

Human gastrin response to secretin after vagotomy

The gastrin response to a liquid meal with and without secretin infusion was studied in nine patients undergoing selective or truncal vagotomy with pyloroplasty for duodenal ulcer disease. Fasting gastrin levels were significantly increased in eight of nine patients after vagotomy, but secretin infusion did not consistently suppress these basal gastrin levels either pre- or postoperatively. Infusion of secretin did significantly lower the integrated gastrin response to feeding both pre- and postoperatively in eight of nine patients. Vagotomy alone did not significantly alter the integrated gastrin response to feeding. This data gives evidence that secretin infusion remains a helpful diagnostic test, differentiating those patients with recurrent ulcer and elevated gastrin levels postvagotomy from those patients with occult Zollinger-Ellison syndrome.

Investigation of exocrine pancreatic function by continuous infusion of caerulein and secretin in normal subjects and in chronic pancreatitis.

Exocrine pancreatic function has been evaluated in 24 controls and 29 patients with confirmed chronic pancreatitis by continuous infusion (90 min) of synthetic caerulein, 100 ng/kg/h, plus GIH secretin, 1 CU/kg/h. Mean secretory values of the controls were comparable to those obtained by others using maximal doses of secretin and CCK. Unlike the controls, patients suffering from chronic pancreatitis demonstrated a progressive reduction in secretion during infusion. Thus, the comparison of responses for the final 30-min period gave much clearer and more complete discrimination between normal and abnormal pancreatic function than the preceding 30-min period.

Plasma Insulin Concentration During Physiological Variations in Immunoreactive Plasma Secretin

The effect of endogenous and exogenous secretin on fasting plasma insulin and glucose concentrations in peripheral venous blood was studied. In 10 non-diabetic subjects intragastric instillation of 300 ml 0.1 mol/l hydrochloric acid increased the plasma secretin concentration significantly. This increment did not influence insulin or glucose concentration. Control experiments with intragastric instillation of 300 ml of isotonic saline did not influence the plasma concentration of secretin, insulin or glucose. In four other non-diabetic persons no significant changes were found in plasma insulin or glucose concentration during an i.v. infusion of pure natural porcine secretin in doses of 0.1, 0.3, 1.0 and 3.0 clinical units/kg/h. The results suggest that secretin is without effect on insulin secretion in the fasting normal subject.

Continuous Secretin Infusion with Pancreozymin Pretreatment as a Pancreatic Function Test

This paper deals with a pancreatic function test with the submaximal dose of secretin given by continuous infusion after injection of cholecystokinin-pancreozymin (CCK-PZ) in the submaximal dose. The active elimination of bladder bile by CCK-PZ pretreatment decreased the influence of biliary contamination, and the volume output and the bicarbonate concentration were stabilized by the continuous infusion of secretin. As a result, the coefficients of variation in the volume output and the bicarbonate concentration were calculated to be about 15 and about 5%, respectively. These variations were considerably smaller than those obtained in the standard secretin test. Therefore, the present study is expected to improve the diagnostic means for pancreatic excretory dysfunction.

Effects of secretin on insulin secretion and glucose tolerance.

Effects of intravenous (IV) infusion of secretin during IV infusion of glucose were examined in normal men. Secretin was administered according to three schedules: with each schedule a comparable priming dose was delivered in the first minute, but this was followed by a maintained (120 min) infusion of secretin at a relatively high rate, or by maintained infusion at one-third that rate, or by brief (15 min) infusion at the lower rate. The lower infusion rate produced increments in secretin in the blood within the range attainable during endogenous secretion. By comparison with effects of glucose alone each secretin infusion enhanced the increments of immunoreactive insulin in the blood. Enhancement of the early release (0-5 min) of insulin was similar with each type of secretin infusion, but the integrated changes in insulin levels through the total infusion period were related to the total doses of secretin. With each dose of secretin glucose tolerance was improved but the three mean glucose curves observed during infusions of secretin were not distinguishable from one another in spite of widely different integrated insulin responses. Secretin did not modify suppression of immunoreactive glucagon or free fatty acids in the blood during hyperglycemia. The results suggest that the effect of continuous administration of secretin on glucose tolerance is not simply related to its integrated insulinotropic action. It is suggested that the effect may be highly dependent on enhancement of insulin secretion early in the response to glycemia, or that it may be due to effects of secretin on glucose production or disposal which are not mediated by insulin.

Secretion of electrolytes by the pancreas of the anaestetized rat.

1. HCO-3, Na+ and K+ concentrations were measured in bile-free pancreatic juice collected from fasted and fed anaesthetized rats. 2. Resting flow rates averaged 0.62 mul. g-1 .min-1 (fasted) and 2.8 mul. g-1. min-1 (fed) and the mean HCO-3 concentrations, respectively, were 25.8 and 33.3 mM. 3. In fasted rats, instillation of HCl into the duodenum caused flow rate to increase threefold and HCO-3 concentrations to double (66 mM). Intravenous infusion of pure natural (GIH) secretin caused a fivefold increase in flow rate; HCO-3 concentrations, again, doubled (67.5 mM). Infusion of synthetic secretin produced effects essentially the same as those produced by GIH secretin. 4. Infusion of Boots secretin caused a thirteenfold increase in flow rate (8.32 mul.g-1. min-1) but HCO-3 concentrations rose only slightly (43.3 mM). However, following cessation of infusion, when flow rate approximated the maximum obtained with pure secretin, the HCO-3 concentration was much higher (57.2 mM at 3.19 uml.g-1.min-1). In fed animals the responses were similar but maximum flow rates were greater (12 mul. g-1. min-1). 5. Infusion of caerulein produced a secretory rate slightly less than with Boots secretin (5.06 mul. g-1.min-1) and HCO-3 concentrations were plasmalike (30.2 mM); infusion of the synthetic octapeptide of cholecystokinin (OP-CCK) gave similar flow rates and HCO-3 concentrations. 6. Infusion of a mixture of caerulein and GIH secretin mimicked closely the effect of Boots secretin. At maximum flow rates (7.6 mul. g-1. min-1) the HCO-3 concentration was 43.7 mM and at lower flow rates (3.90 mul.g-1. min-1) it rose to 54.2mM. 7. It is concluded that the response of the rat pancreas to secretin is qualitatively similar to that of all other vertebrates so far studied, but, relative to other animals, the response is sluggish. In contrast, the rat pancreas responds well to cholecystokinin (CCK) stimulation, yielding a juice with plasma-like HCO-3 concentration. Boots secretin, which is heavily contaminated with CCK, causes a mixed response resembling that of CCK at high secretory rates and that of pure secretin at lower rates. 8. An unexplained feature of rat pancreatic juice was that K+ concentrations, although plasma-like in unstimulated samples, rose to about 8mM when flow rate increases as a result of secretin, but not CCK, stimulation. In all other animals so far studied, the K+ concentration has been found to be independent of flow rate.

Gastric Operations and Glucose Homeostasis: II. Glucagon and secretin

Alimentary hyperglycemia in patients who have undergone gastric operations may be due, in part, to altered intestinal signals for glucose disposition. We measured glucose, immunoreactive insulin (IRI) pancreatic glucagon (IRG), and glucagon-like immunoreactivity (GLI) after oral glucose in patients with prior antrectomy or vagotomy and pyloroplasty and in normal individuals. All subjects had normal assimilation coefficients for intravenous glucose, which suggests that the responsiveness of the pancreatic beta-cells had not been altered by the surgical procedures. The early hyperglycemic response to oral glucose and the associated elevation of plasma GLI were much greater and the IRI levels slightly higher in both experimental groups in comparison to normal subjects. A decrease in the level of IRG, albeit not statistically significant, was noted in all groups after the ingestion of glucose. In gastrectomy patients, secretin infusion during repeated oral glucose tolerance tests partially corrected the hyperglycemia and lowered plasma GLI and IRI levels. The responses of the vagotomy and pyloroplasty patients and of the normal subjects were not altered by secretin infusion. We conclude that the intolerance or oral glucose after gastric surgery may be related to elevated GLI levels, and that the beneficial effect of secretin may be due to its ability to decrease these levels.

Effect of secretin on electrical activity of small intestine.

The effect of intravenously administered secretin (0.5, 2.0, 6.0 U/kg-h) and intraduodenal acidification (13.2 meq/h HCl) on the electrical activity of the small bowel of three conscious dogs with gastric and duodenal cannulas was observed. Electrical activity was recorded in fasted as well as fed conditions through silver wire electrodes implanted along the entire length of the small bowel. Intravenous infusion of secretin in all dosages and in all dogs delayed the onset of the interdigestive myoelectric complex and reduced the total percentage of slow waves with superimposed spike potentials. Intraduodenal acidification also inhibited the interdigestive myoelectric complex, which developed incompletely with fewer action potentials on slow waves. Secretin did not produce any alteration in the fed pattern of activity, slow-wave frequency, or the caudal migration of the interdigestive myoelectric complex. The present study indicates that the nuerohumoral mechanisms responsible for initiation of the interdigestive myoelectric complex may be different from those responsible for its caudal migration.

Secretin effect on gastrin, gastric secretion in dogs with chronic antral stimulation

Antrocolic transposition in four dogs with Heidenhain pouch and gastrojejunostomyresulted in a marked increase in fasting plasma gastrin concentration and sustained highacid secretion, closely related to gastrin levels. A marked production of pepsin output could not be correlated with plasma gastrin. Reduction in plasma gastrin concentration was more than twofold less pronounced than the reduction in acid output for 1 and 2 U/kg-h, while the 0.5 U/kg-h no effect was noted. For both acid output and gastrin concentrations, close correlations were noted between presecretion level and remaining level upon secretin infusion. Despite the reduction in the secretory volume of the pouch, 0.5 and 1 U/kg-h of secretin induced a 1.5- and 2-fold increase in pepsin output, respectively. Two untis per kilagram-hour decreased the secretory volume as well as the pepsin output. If the physiological release of secretin in dogs does not exceed the equivalent of the lowest dose studied, our results would indicate that acid inhibition is a physiological activity of secretin, while the effect on circulating gastrin concentration seems to be phamacological.

Effect of extragastric and truncal vagotomy on pancreatic secretion in the dog.

In four dogs with chronic pancreatic and gastric fistulas, dose-response studies of pancreatic bicarbonate and protein secretion were done with intravenous infusions of secretin, octapeptide of cholecystokinin (OP-CCK), and 2-deoxyglucose (2-DG). The pancreatic response to a meal and to duodenal perfusion of graded concentrations of HCl, sodium oleate, and tryptophan were also studied. These observations were repeated after division of both the hepatic and celiac vagal branches to produce extragastric vagotomy, and subsequently after transthoracic truncal vagotomy. The responses to secretin, OP-CCK, and to duodenal perfusion of HCl were either unaltered or only slightly decreased by either extragastric or truncal vagotomy. Basal pancreatic secretion and the responses to duodenal perfusion of oleate and tryptophan were markedly depressed by extragastric vagotomy. These findings indicate that tonic vagal activity contributes to basal pancreatic secretion but has little effect on the response of the pancreas to secretin or CCK or on the release of secretin from the intestine. The decreased pancreatic response to intestinally perfused oleate and tryptophan seen after extragastric vagotomy could be caused either by interruption of reflex paths between gut and pancreas or by interference with CCK release. Extragastric vagotomy reduced pancreatic responses to a meal and to 2-DG and subsequent truncal vagotomy caused still further reduction, possibly, at least in part, by depressing release of antral gastrin.

Effect on Insulin Output and Pancreatic Blood Flow of Glucagon, Secretin, Tolbutamide and Thiocid Infusions into an In Situ Isolated Portion of Pancreas

Effects on blood flow and insulin output of the infusion of glucagon, secretin, tolbutamide and thiocid were studied on an isolated portion of dog pancreas with only one afferent and one efferent blood vessel remaining. Glucagon infused at the rate of 1 µg per minute initially gave a significant increase in pancreatic blood flow and insulin output. Infusion of glucagon at the rate of 10 µg per minute gave a significant increase in pancreatic blood flow and insulin output initially and throughout the infusion period. Secretin infused at the rate of 0.2 Unit per minute initially gave a significant increase in pancreatic blood flow and no significant change in insulin output. Infusion of secretin at the rate of 1.0 Unit per minute gave a significant increase in pancreatic blood flow and a highly significant increase in insulin output initially and throughout the infusion period. Tolbutamide infused at the rates of 0.6 and 3.0 mg per minute gave no change in pancreatic blood flow but increased the insulin output significantly. Thiocid (the preservative for tolbutamide) infused at pH 7.0, 8.5 and 9 gave no change in pancreatic blood flow or insulin secretion.

Calcium and secretin-stimulated gastrin release in the Zollinger-Ellison syndrome.

Abstract Serum gastrin and calcium concentrations were measured and compared before and after calcium and secretin infusions in three patients with the Zollinger-Ellison syndrome and three control ...

The role of secretin in the inhibition of gastric secretion by intraduodenal acid.

The effect of intraduodenal acid on pentagastrin-stimulated gastric secretion has been investigated in 12 normal subjects and 23 patients with chronic duodenal ulceration. Plasma secretin levels were monitored during each test using a highly sensitive radioimmunoassay. Significant inhibition of gastric secretion occurred in the normal subjects and duodenal ulcer patients. A significant rise in plasma secretin was observed in both groups after intraduodenal acid though there was a complete lack of correlation between the magnitude of the secretin response and the degree of gastric inhibition. Ten subjects received intraduodenal acid and a subsequent intravenous infusion of exogenous secretin (0.125-0.25 units/kg over six minutes). Gastric inhibition occurred after the acid instillation but not after secretin infusion despite plasma secretin levels greatly in excess of those produced by intraduodenal acid. These results suggest that release of secretin by itself cannot explain the gastric inhibitory response to intraduodenal acid in man.

Effect of Intragastric Administration of Alcohol on the Ethanol Concentrations and Osmolality of Pancreatic Juice, Bile, and Portal and Peripheral Blood

The effect of intragastric administration of alcohol on the concentration of ethanol and osmolality of portal blood, peripheral blood, and pancreatic and biliary secretions was investigated in anesthetized dogs. Pancreatic secretion was stimulated by a constant intravenous infusion of secretin. Under the conditions of the experiment, and with the doses of ethanol used (priming dose and the subsequent constant infusion), the ethanol concentration of these fluids reached a steady state 25 min after the administration of the priming dose of ethanol. The mean steady state concentration of ethanol in the portal blood was significantly higher (P

The role of vagal innervation in gastric and pancreatic responses to meals varying in pH.

In three dogs provided with chronic gastric and pancreatic fistulae, gastric acid response to a peptone meal was measured by a method of intragastric titration at pre-selected pH values ranging from 6.0 to 2.0 or at a constant pH during intravenous infusion of secretin in graded doses ranging from 0.25 to 4.0 u./kg.hr. Simultaneously, pancreatic secretion was determined by the standard collection technique and serum gastrin response was measured by radio-immunoassay. In this way the pH profile for the inhibition of gastric response and stimulation of pancreatic secretion as well as serum gastrin response to a peptone meal have been determined and compared with that obtained with exogenous secretin or feeding a liver meal. Truncal vagotomy resulted in a significant decrease of gastric acid response to the meal at all pH levels or at all doses of secretin but the inhibitory effect of gastric acidification or secretin on serum gastrin and gastric acid response to a meal remained unchanged. Vagotomy caused a decrease of pancreatic secretory response to meals at all pH levels and at all doses of secretin except the largest one. Pancreatic secretion stimulated by secretin alone was not affected by vagotomy, whereas that induced by feeding a liver meal was markedly decreased by this procedure. From these studies we have tentatively concluded that the vagus nerve facilitates the release of intestinal hormones and that vagotomy causes a decrease of gastric and pancreatic responses to endogenous but not to exogenous stimuli.

The kinetics of pancreatic amylase secretion and its relationship to volume flow and electrical conductance in the anaesthetized cat.

1. Enzyme secretion in response to short duration vagal stimulation or to rapid I.V. injections of cholecystokinin-pancreozymin (CCK-PZ) or gastrin or to intra-arterial injections of acetylcholine is a function of the volume of juice secreted and not primarily a function of time.2. The output of amylase in response to each stimulus occurred in a constant volume of approximately 15 drops (0.5 ml.) regardless of the rate of background secretin stimulated flow of water and electrolyte.3. It is argued that because amylase secretion occurs in this constant volume, it is due to the rapid secretion of enzyme into the duct system from the acini, and subsequently the secretin stimulated secretion of water and bicarbonate washes the enzyme from the duct system.4. When enzyme secretion is stimulated an increase in the electrical conductance (measured at 1.592 kHz) occurs across the tail of the pancreas. This increased conductance has two components. An early peak associated with the extrusion of enzyme from the acinar cell and a later peak which is probably due to vasodilatation.5. Atropine was without effect on both enzyme secretion and the conductance record when the stimulant was CCK-PZ. Atropine blocked enzyme secretion and both peaks of the conductance record in response to stimulation by acetylcholine. Atropine blocked enzyme secretion and abolished the early phase of the conductance record, on vagal stimulation. It was without effect on the later peak which probably indicates an atropine resistant vasodilation of the pancreatic vessels.6. When the vagus is stimulated on a background of submaximal electrolyte secretion caused by the intravenous infusion of secretin, the volume rate of secretion and the rate of amylase secretion follow a similar time course. The maximal volume response occurred between 7 Hz and 15 Hz and the maximal amylase output per impulse was at 5 Hz.

Gastro-intestinal hormones and bile secretion in the perfused pig liver: the effects of secretin, cholecystokinin and pentagastrin.

The effects of secretin, cholecystokinin and pentagastrin on the hepatic bile secretion rate were studied in the perfused pig liver. An increase in the bile secretion rate and bicarbonate output was found during secretin infusion. Simultaneous infusion of either cholecystokinin or pentagastrin with secertin augmented this increase to level greater than the sum of the single hormone responses. Secretin produced a fall in bile‐salt output. but neither cholecystokinin nor pentagastrin had any such effect. However, when either cholecystokinin or pentagastrin was infused together with secretin, there was an increase in bile salt output for 30 minutes, followed by maintenance of output at base‐line values. All three hormones must therefore influence the handling of bile salts by the hepatocyte.

The effects of intestinal vasodilator mechanisms on the rate of 85Kr absorption in the cat.

AbstractThe absorption rate of 85Kr from the small intestine of the cat was estimated during intestinal vasodilatation induced by transmural electrical field stimulation or by local i.a. infusions of cholecystokinin and secretin. As blood flow increased, a considerably augmented rate of absorption was observed, the absorption rate being increased in excess of that observed during corresponding hyperemia induced by isopropylnoradrenaline. An increased fraction of the intramural blood flow became fully equilibrated with luminal contents during the vasodilatory procedures.

Studies on the elimination of secretin and cholecystokinin with regard to the kinetics of exocrine pancreatic secretion.

Studies were performed on 72 anesthetized mongrel dogs. Upon injection or infusion of secretin into the portal vein, the pancreatic volume and bicarbonate response was found to be significantly smaller than following administration into the femoral vein, but only when low doses of secretin (0.25 clin U/kg/h or smaller) were applied. No difference was observed in pancreatic protein and enzyme secretion after cholecystokinin, when both high and low doses were applied to the portal or femoral vein. The injection of secretin and cholecystokinin into the renal artery causes a loss of biological activity of 75 and 60%, respectively, as compared to femoral administration. Ligature of the blood vessels of both kidneys resulted in an increase in the biological activity of secretin of 80% and of cholecystokinin of 50%. The slopes of the flow rate curves determined upon secretin injection were smaller after ligature of the renal blood vessels. The biological half-life of secretin increased from an average of 2.9 to 4.8 min. These results indicate that the kidneys play a role in the catabolism of exogenous secretin and cholecystokinin, whereas the blood and the liver (at least for cholecystokinin) seem to be of small importance.

The effect of secretin on glucose-stimulated insulin secretion in man.

The effect of physiological dose of purified secretin on glucose-stimulated insulin secretion was studied in healthy volunteers during a continuous infusion of glucose. The intravenous injection of ten unit of secretin during the infusion of glucose caused a greater rise in plasma insulin level and a more marked decrease in blood glucose concentration than either the infusion of glucose or secretin alone did, resulting in a significant increase in the insulinogenic index. One unit of secretin has no effect on plasma insulin and glucose concentrations in the fasting or hyperglycemic state.The physiological role of secretin in regulating insulin secretion after ingestion of food was discussed.