Exocrine and endocrine pancreatic function were studied simultaneously in the isolated perfused pancreas from rats fed a normal or an acarbose-containing diet (150 mg/100 g food) for 20 days. Body weight gain of acarbose-treated rats was slightly lower than that of control rats, despite a larger food intake. Basal and caerulein-stimulated flow rates of pancreatic juice from acarbose-treated rat pancreases were similar to those from controls, suggesting that the treated rat pancreas has normal sensitivity and responsiveness to caerulein. On the other hand, amylase output in response to caerulein was significantly decreased in acarbose-treated rat pancreases, though basal output was normal. The addition of acarbose to the diet for 20 days had no effect on the speed of the insulin response to glucose and caerulein, but the magnitude of insulin secretion to glucose stimulation was reduced by 40% and the caerulein-induced additional output of insulin by 30% in the treated group as compared with the control group. The present investigation has demonstrated that inhibition of key enzymes for carbohydrate digestion decreases not only the secretory responsiveness of amylase from acinar cells to caerulein stimulation but also the sensitivity of the insulin-secretory mechanism of pancreatic B cells to glucose and non-glucose stimulation.

Acarbose↗

PubMed1983

Exocrine and endocrine pancreatic function in rats treated with alpha-glucosidase inhibitor (acarbose).

Pancreatic exocrine and endocrine secretory dynamics were studied in the isolated perfused pancreata of rats fed a normal diet or a diet supplemented with the alpha-glucosidase inhibitor, acarbose (150 mg/100 g food). After 10 days, the body weight of acarbose-treated rats was slightly lower than that of the control rats despite a larger food intake. Pancreatic amylase levels were significantly decreased, trypsinogen levels were significantly increased, and lipase levels were unaltered in the treated group compared with the controls. Basal and caerulein-stimulated flow rates of pancreatic juice as well as basal amylase output were similar in both groups, whereas caerulein-stimulated amylase output was significantly lower in the acarbose-treated group. Secretory responsiveness of amylase in the treated group was, however, about twice as high as that in the control group when related to pancreatic amylase content. Insulin release in response to either glucose or cerulein was similar in both groups. These findings indicate that treatment with acarbose may alter pancreatic enzyme content without changing the secretory responsiveness of either the exocrine or endocrine pancreas.

Acarbose↗

PubMed1983

Amylase secretion by isolated pancreatic acini after chronic cholecystokinin treatment in vivo.

Rats were given subcutaneous injections of synthetic cholecystokinin octapeptide (CCK8, 5 micrograms/kg) in a depot carrier twice daily for 7-14 days. The pancreatic wet weight increased by 20.6 and 30.9% in the rats treated with CCK8 for 7 and 14 days, respectively. The increase in pancreatic weight was associated with an increase in the amount of protein per DNA, indicating hypertrophy of the acinar cells, and with an increase in the total amount of pancreatic DNA. Moreover, CCK administration also increased the amylase content per DNA. In acini prepared from CCK8-treated rats, responsiveness to CCK8 was increased when amylase release was expressed relative to DNA but was decreased when calculated as the percentage of the initial content in the acini. The dose-response curves for CCK8 were similarly shaped in both CCK8-treated and control rats, but they were shifted 3- to 10-fold toward higher concentrations of CCK8 after 7 and 14 days of CCK8 treatment. There were no major changes in the affinity and capacity of CCK receptors determined by studying the binding of radioiodinated CCK, suggesting that alterations in pancreatic amylase release were due to changes at a postreceptor loci. In support of this hypothesis, the secretory response to carbachol, known to act on a different receptor but by a common intracellular mechanism, was altered in a manner identical to the response to CCK8. Thus chronic stimulation with CCK sufficient to induce pancreatic hypertrophy does not greatly alter CCK receptors and induces only moderate postreceptor desensitization.

Amylases↗

PubMed1983

Effects of C-terminal fragments of cholecystokinin on exocrine and endocrine secretion from isolated perfused rat pancreas.

The ability of various C-terminal fragments of cholecystokinin (CCK) to increase pancreatic exocrine and endocrine secretion was examined in the isolated perfused rat pancreas. CCK octapeptide (CCK-8) induced biphasic dose-response curves for stimulation of pancreatic juice and amylase secretion. Maximal pancreatic juice and amylase output were obtained with 100 pM CCK-8. Concentrations of CCK-8 that caused pancreatic exocrine secretion also increased insulin release in the presence of 8.3 mM glucose. The tetrapeptide of CCK also simultaneously stimulated both exocrine and endocrine secretion, but was about 100,000 times less potent than CCK-8. By contrast both deca- and tetradecapeptide of CCK at a concentration of 100 pM stimulated secretion of pancreatic juice and amylase, and elicited insulin release comparably to CCK-8. The complete CCK-8 sequence was required as deamidated CCK-8 was without effects on exocrine and endocrine pancreatic secretion at a concentration of 100 pM. The present observations suggest that the structural requirements for CCK-induced insulin secretion are the same as those for CCK-induced exocrine secretions, and that the amino acids in position 5-8 and the amidated residue on the C-terminus are required for physiological activity of CCK on both the exocrine and endocrine pancreas. It is concluded that C-terminal fragments of CCK with eight or more amino acid residues are potent potentiators of insulin release as well as pancreatic exocrine stimulants.

Amylases↗

PubMed1983

Direct modulation of pancreatic CCK receptors and enzyme secretion by insulin in isolated pancreatic acini from diabetic rats.

The effect of insulin on pancreatic enzyme secretion was studied in vitro by using isolated pancreatic acini prepared from rats rendered diabetic with streptozotocin. Preincubation of acini with insulin increased the maximal release of amylase and ribonuclease in response to CCK8 but not to carbamylcholine, a secretagogue acting via a different receptor. Insulin by itself had no effect on enzyme release. The effect of insulin was time dependent and increased up to 2 h, the longest time studied. An effect was observed at 1 nM insulin and the maximal effect was observed at 100 nM. The properties of CCK receptors on the acini were studied using biologically active 125I-BH-CCK33. Insulin pretreatment decreased both the affinity of the high-affinity CCK receptors and the capacity of the low-affinity CCK receptors. Within the framework of the current model, in which occupancy of high-affinity CCK receptors stimulates and low-affinity receptors inhibits amylase release, the change in receptors induced by insulin could account for the altered enzyme secretion. Thus, insulin appears to have a direct effect to regulate CCK receptors and CCK-induced secretion in isolated pancreatic acini.

Amylases↗

PubMed1983

[Relationship between the severity of diabetes mellitus and pancreatic exocrine dysfunction].

Explore the source record for details and available documents.

Amylases↗

PubMed1982

Salivary-type hyperamylasemia in primary lung cancer: observation of a possible precursor of the salivary-type isoamylase.

Although recent studies by column chromatography and electrophoresis showed that elevated amylase activity in the body fluids and tumor extracts in patients with primary lung cancer was mainly in the salivary-type isoamylase, neither mechanism nor mature of elevation of amylase have been clarified yet. This study was undertaken in order to make clear the nature of amylase elevated in the body fluids and tumor extracts of patients with primary lung cancer. In addition, amylase contained in the extracts of normal lungs and diseased lungs of patients who had died of various diseases was also studied. Our results revealed that amylase elevated in the body fluids and tumor extracts in patients with primary lung cancer was the salivary-type isoamylase and, moreover, that small amounts of salivary-type isoamylase in normal lung tissues and large amounts in diseased lung tissues were also contained. These facts suggested that salivary-type isoamylase was physiologically contained in normal lung tissues and large amounts in diseased lung tissues were also contained. These facts suggested that salivary-type isoamylase was physiologically contained in normal lung tissues and might be activated through pathological processes, such as inflammation, circulatory disturbance or tumor formation. Two peculiar isoamylases with cathodic mobility on polyacrylamide gel electrophoresis were found. One of them was so unstable that it was converted to the stable salivary-type isoamylase, suggesting the precursor of human salivary isoamylase.

Adenocarcinoma↗

PubMed1982

Protein synthesis inhibitors enhance secretagogue sensitivity of in vitro rat pancreatic acini.

Isolated rat pancreatic acini were treated with cycloheximide and amylase release was measured. This agent increased the sensitivity to both synthetic octapeptide of cholecystokinin (CCK8) and carbamylcholine, the major secretagogues known to utilize Ca2+ as a second messenger. The mechanism of the cycloheximide effect was via inhibition of protein synthesis, as indicated by the following: 1) the concentration of cycloheximide used inhibited leucine incorporation by greater than 90%; 2) this effect was not instantaneous but increased up to a 2-h pretreatment; and 3) a similar effect was obtained with puromycin, a chemically different inhibitor of protein synthesis. Cycloheximide acted on the steps by which secretagogues mobilize cellular Ca2+ because the dose-response curve for 45Ca2+ efflux was shifted to the same extent as that for amylase release, whereas the dose-response curve for amylase release induced by the Ca2+ ionophore A23187 was not altered. The results suggest, therefore, that a rapidly turning-over protein present in pancreatic acinar cells exerts an inhibitory influence on Ca2+ mobilization by secretagogues.

Amylases↗

PubMed1982

Effect of diabetes mellitus on the regulation of enzyme secretion by isolated rat pancreatic acini.

The nature and mechanism of the pancreatic exocrine dysfunction in diabetes mellitus were evaluated in vitro using isolated pancreatic acini prepared from streptozotocin-induced diabetic rats. The content of amylase and ribonuclease in diabetic acini was approximately 0.5 and 50% of the normal content, respectively. Further, reduced amounts of both enzymes were secreted by diabetic acini in response to both cholecystokinin (CCK) and carbamylcholine. However, when enzyme secretion was normalized relative to initial acinar contents, both normal and diabetic acini released enzymes at a comparable maximal rate. The time course of the release of these enzymes, and newly synthesized protein were similar in both acini. In normal acini, the effect of CCK was maximal at a concentration of 100 pM; higher concentrations led to submaximal enzyme release. The dose-response curve in diabetic acini was similarly shaped, but shifted three-fold towards higher concentration. The mobilization of cellular Ca(2+) in response to CCK was also shifted. In contrast to these results with CCK, the dose-response curve to carbamylcholine was unaltered by diabetes. The observed effects were confirmed to be due to insulin deficiency and not due to direct toxic effect of streptozotocin on acinar cells or malnutrition. Streptozotocin had no acute effect on acini when measured 24 h after administration, and alloxan, another beta cell toxin, induced similar changes in acinar enzyme content and secretory response. Moreover, the administration of exogenous insulin to diabetic rats returned the content of pancreatic amylase and the secretory response to CCK towards normal. Starvation for 48 h, although inducing a significant weight loss, did not mimic the effects of diabetes. The present studies demonstrate two major abnormalities in pancreatic exocrine secretion in the diabetic rat: (a) the content of certain digestive enzymes is markedly altered, leading to an altered amount of zymogen secretion, (b) the sensitivity to CCK is selectively reduced, most likely related to a defect in receptor activated transmembrane signaling.

Acetylcholine↗

PubMed1982

Glucose-dependent insulinotropic action of cholecystokinin and caerulein in the isolated perfused rat pancreas.

The effect of pure natural porcine cholecystokinin (CCK) and synthetic caerulein on endocrine and exocrine pancreatic secretion was investigated in the isolated perfused rat pancreas in the presence of physiological concentrations of glucose. CCK (0.25 mU/ml) or caerulein (0.01 ng/ml) potentiated the insulin secretion induced by 5.6 mM glucose; a significant increase in pancreatic exocrine secretion was also observed at these doses of CCK or caerulein. Further increases in the concentration of CCK (0.25 to 1 mU/ml) or caerulein (0.01 to 1 ng/ml) resulted in dose-dependent increases in both insulin and pancreatic exocrine secretion. The effectiveness of CCK and caerulein as insulinotropic agents depended on the glucose concentration; they were more effective at higher concentrations of glucose. Thus, CCK or caerulein significantly and coincidentally stimulated both insulin secretion and pancreatic exocrine function if 5.6 mM or more glucose is present, whereas in previous studies using 2.8 mM glucose, stimulation of insulin secretion was elicited only with concentrations of the peptides supramaximal for an effect on pancreatic exocrine secretion. CCK may contribute to the entero-insular axis.

Amylases↗

PubMed1982