The Effect of the Intrapancreatic Calcium and Glucagon Administration on the Somatostain-Induced Inhibition of Insulin and Glucagon Secretion in Dogs

Abstract

We made a study to determine if calcium and glucagon have an effect on insulin secretion, which is inhibited by somatostatin in normal dogs.After an over-night fast, six mongrel dogs weighing 15 to 32 kg were anesthetized with an intravenous administration of sodium pentobarbital.Calcium (0.8 mg/kg.b.w. of CaCl2) and glucagon (10-1 mg) were injected into the superior pancreaticoduodenal artery under the infusion of saline (1 ml/min) or cyclic somatostatin (50 μg bolus plus 5 μg/ml/min) through the pancreatic artery in 6 normal anesthetized dogs. Levels of plasma immunoreactive insulin (IRI) and glucagon (IRG) were estimated in the pancreatic vein and femoral artery by using the double antibody method and canine insulin standard and by employing anti-glucagon antibody AJ 15 (which crossreacted with glucagon-like immunoreactivity) and the method of dextran-coated charcoal. The saline and somatostatin infusions were conducted on the same dog at 20 minute intervals. Blood samples were collected from the pancreatic vein every 5 seconds for 2 minutes and thereafter every 1 min until 5 minutes had elapsed and from the femoral artery every 1 min.The results were the following : 1. The calcium levels of the pancreatic vein increased from 4 to more than 8 mEq/L within one minute, whereas those of the femoral artery did not change significantly. 2. Under the saline infusion, CaCl2 evoked a sharp rise in the pancreatic venous IRI levels which started 25 seconds after the injection, rose to a peak of thirteen folds from baseline at 40 seconds and lasted for almost 2 minutes, whereas under the somatostatin infusion, the peak level was reached at 55 seconds and affected only one third of those under the saline infusion. 3. IRG levels in the pancreatic vein under the saline infusion did not show any significant changes after the CaCl2 injection and were higher than those under the somatostatin infusion at all points. 4. Under the somatostatin infusion, 10-1 mg of glucagon did not induce any rise at all in IRI concentrations of the pancreatic vein. But when CaCl2 was given just before the glucagon administration, a slight but significant rise in IRI was observed.It is concluded that, in vivo, calcium has an insulin secretory effect under a normoglycemic state, and that somatostatin has an inhibitory action on both calcium- and cyclic-AMP-mediated insulin release.