Abstract
In the present study, we examined the direct effect of glucose, especially at physiological levels, catecholamine and tolbutamide on somatostatin secretion from isolated rat pancreatic islets prepared by collagenase digestion.
The rats which had been not fasted prior experiment were anesthetized with Nembutal and the pancreatic islets were isolated by method of Lacy and Kostianovisky with some modification. After the preincubation 10 isolated islets were incubated in Krebs Ringer Bicarbonate buffer 1.0 ml containing 0.1% BAS and 1000 KIE of aprotinin under the gas phase of 95% O2 and 5% CO2 for 30 minutes, adding the agents to be studied.
Released somatostatin was determined by radioimmunoassay system utilizing a rabbit antiserum (B-5) obtained following immunization with synthetic somatostatin. Synthetic Nα-tyrosylated somatostatin labelled with 125I using the lactoperoxidase method and purified on a Sephadex G-10 column was used as the tracer.
The levels of released somatostatin into medium were above the sensitivity limits of the assay at a glucose concentration of 50 mg/dl (8.4±0.7pg/islet/30 min.). With increasing concentrations of glucose (between 50 and 400 mg/dl), there is a progressive increase in the rate of somatostatin secretion which reaches a maximum rate at 300 mg/dl, about 3 times the basal output. DL-Epinephrine (0.1μM) did not have a significant effect on glucose induced somatostatin secretion, although it significantly inhibited glucose induced insulin release. The inhibitory effect of epinephrine on insulin release was removed by addition of phentolamine, but somatostatin secretion was not affected. Tolbutamide significantly enhanced somatostatin release at glucose concentrations of both 50 and 200mg/dl, as well as the expected release of insulin.
These results indicated that, like insulin, pancreatic somatostatin might respond at approximately 100 mg/dl of glucose and above, perhaps directly stimulated by glucose and exert an important physiological role in glucose homeostasis, that tolbutamide induced a somatostatin secretion both at low and high glucose concentration along with an insulin secretion and might exert as antihyperglycemic action, in part, not only through the insulin release but also through the secretion of somatostatin. The effect of catecholamine on pancreatic somatostatin secretion remained to be elucidated.
