Amylase Secretion In Pancreatic Acini Research Articles

Inositol trisphosphate independent increase of intracellular free calcium and amylase secretion in pancreatic acini

It is generally believed that the activation of various cell surface receptors results in the phospholipase C-catalyzed production of inositol trisphosphate which, in turn, increases the intracellular concentration of free Ca 2+ by stimulating its release from non-mitochondrial sources. We have investigated both the production of inositol trisphosphate and changes in intracellular Ca 2+ concentration in rat pancreatic acini in response to caerulein and CCK-JMV-180, two analogs of cholecystokinin. Both of these analogs cause comparable increases in the rate of amylase secretion and in intracellular Ca 2+ concentration but their effects on inositol phosphate generation are dramatically different; caerulein stimulates significant production of inositol phosphates within 1 min of its addition, whereas no detectable levels of inositol phosphates were generated within the same time after addition of CCK-JMV-180. These results suggest that the CCK-JMV-180 stimulated release of intracellular Ca 2+ is not mediated by inositol trisphosphate but some other as yet unidentified messenger.

Suppression of secretagogue‐induced amylase secretion in pancreatic acini of cold‐exposed rats.

1. The influence of prolonged exposure to a low ambient temperature on the pancreatic exocrine function was investigated in rats. Amylase concentration in acini prepared from rats housed at 5 degrees C for 2 weeks was specifically and dramatically reduced. The enzyme activity relative to acinar DNA concentration was only 48% of that of control acini obtained from rats reared at the thermoneutral temperature of 25 degrees C. Amylase content relative to acinar protein concentration also decreased by 35%. In contrast, acinar trypsinogen content relative to protein concentration increased to 161% of that of control acini. No comparable change was found in the parotid glands. 2. In acini from cold-exposed rats, amylase release in response to cholecystokinin octapeptide or carbamylcholine was simultaneously reduced when expressed relative to acinar DNA or protein concentration and the dose-response curve shifted downward. However, when the secretory responsiveness of amylase was represented as a percentage of initial acinar enzyme content, the observed decrease disappeared and the dose-response curve was unaffected by cold exposure. 3. Secretagogue-stimulated trypsinogen release was augmented in acini from cold-exposed rats when expressed per acinar protein concentration. Conversely, its percentage release was slightly lowered but the release per acinar DNA concentration remained unaltered. 4. Pancreatic insulin concentration normalized to tissue wet weight or protein concentration was unaffected by prolonged cold exposure but the plasma insulin concentration significantly decreased by 45% as compared with that of thermoneutral rats. 5. Chronically administered exogenous insulin partially restored the decreased acinar amylase concentration in cold-exposed rats. The dose-response curve for amylase normalized by acinar DNA or protein content also tended to be shifted upward by insulin treatment. Acinar trypsinogen concentration in these rats was not significantly altered from that in cold-exposed, non-insulin-treated rats. Percentage release of each enzyme was decreased by exogenous insulin. 6. Cold-induced suppression of pancreatic acinar amylase concentration, resulting in a proportional decrease in secretory responsiveness, was confirmed at the cellular level. Insulin deficiency at a low ambient temperature is likely to be a major cause of cold-induced suppression of amylase biosynthesis and its release via an insulin-pancreatic acinar axis.

Augmentation of secretagogue‐induced amylase secretion in pancreatic acini of heat‐exposed rats.

1. The effects of prolonged heat exposure on pancreatic exocrine secretion were investigated to evaluate the involvement of the insulin-pancreatic acinar axis. Rats were kept at 34 degrees C and a relative humidity of 40% for 2 weeks with or without insulin administration. Control rats were housed at the thermoneutral temperature of 25 degrees C. By using isolated acini, secretory function was examined at the cellular level. 2. Without insulin treatment, acinar amylase concentration, expressed per microgram of cellular protein, was increased by heat exposure, while trypsinogen concentration, expressed per microgram of acinar DNA, decreased. The ratio of acinar amylase to trypsinogen increased significantly from 2.82 to 5.69 by prolonged heat exposure. With insulin treatment, the heat-induced increase in amylase activity was lessened but the decrease in trypsinogen remained unchanged. The ratio was somewhat lessened to 4.66. 3. In acini from saline-treated rats, amylase release in response to varying concentrations of cholecystokinin octapeptide or carbamylcholine was significantly augmented by prolonged heat exposure. As a result, the dose-response curve shifted upwards. However, in acini from insulin-treated rats, the increase in secretory response was lessened, similar to the effect on acinar content. On the other hand, changes in trypsinogen release were not as notable as those in amylase release. The ratio of amylase to trypsinogen in pancreatic juice released by 100 pM-cholecystokinin octapeptide increased from 1.56 to 3.04 in saline-treated rats and from 1.60 to 2.34 in insulin-treated rats. 4. In heat-exposed, saline-treated rats the plasma concentrations of glucose and insulin were significantly elevated, while in insulin-treated rats these increases were lessened and the elevation of plasma insulin concentration was no longer significant. 5. It is suggested that heat exposure elevates resting plasma glucose concentration, probably because of decreased metabolic activity, which results in a concomitant rise in plasma insulin concentration. This hormonal change most likely is a major cause of augmentation of acinar amylase synthesis and of the resultant potentiation of stimulus-secretion coupling via an insulin-pancreatic acinar axis. Heat exposure modified pancreatic exocrine function in the opposite direction to what occurred in cold-exposed animals. It was confirmed that changes in pancreatic exocrine function via a modification of the insulin-pancreatic acinar axis can actually occur under normal physiological circumstances. From the nutritional point of view, this modification by ambient temperature should be taken into consideration.