The effect of glucose and tolbutamide on immunoreactive somatostatin release from perifused pancreatic islets of normal and streptozotocin diabetic rats.

Abstract

The patterns of immunoreactive somatostatin (IRS) responses to glucose and tolbutamide were investigated in perifused pancreatic islets of both normal and diabetic rats.The incubation chamber of the perifusion apparatus for the islets was devised with a 2.5 ml disposable syringe. By the method of Lacy, the pancreatic islets were isolated from diabetic rats about 30 days after a single intravenous injection of streptozotocin (STZ, 60 mg/kg body weight) and from normal rats of comparable body weight. The fasting blood glucose was 437±3 mg/100 ml in the diabetic rats and 120±5 mg/100 ml in normal ones. The concentration of IRS in each effluent was measured by the specific double antibody radioimmunoassay for somatostatin.During the initial 20 min incubation period with the medium containing 2.8 mM glucose, the levels of IRS were 11.3±1.0 pg/100 islets/2 min in normal islets and 32.0±3.4 pg/100 islets/2 min in diabetic islets. The latter value was significantly higher than the former (p<0.001). IRS levels gradually rose following 16.7 mM glucose and reached the maximal values with 30.2±5.7 pg/100 islets/2 min at 66 min in normal islets and with 56.8±13.3 pg/100 islets/2 min at 88 min in diabetic islets. The levels of IRS in diabetic islets were significantly higher than those of normal islets (p<0.001) throughout the experimental period. In the case of tolbutamide the IRS levels increased promptly to 51.9±6.6 pg/100 islets/2 min in diabetic islets and to 23.7±4.6 pg/100 islets/2 min in normal islets 2 min after initiation of the infusion. The former value was significantly higher than the latter (p<0.001). The levels of immunoreactive glucagon (IRG) in response to tolbutamide were significantly higher in the diabetic islets than in normal islets (p<0.001). These results indicate that there exists a hypersecrecretion of IRS from STZ-induced diabetic rats during the infusion with glucose and tolbutamide.