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Pancreatic somatostatin is a mediator of glucagon inhibition by hyperglycemia

Pancreatic somatostatin is a mediator of glucagon inhibition by hyperglycemia

Diabetes 36(5): 592-596

We have previously shown that a nonimmunoreactive analogue of somatostatin, (D-Ala5, D-Trp8)somatostatin, differentially inhibits pancreatic somatostatin secretion without inhibiting insulin or glucagon secretion. During normoglycemia, suppression of pancreatic somatostatin with this analogue increases glucagon and insulin secretion, suggesting that pancreatic somatostatin tonically inhibits glucagon and insulin secretion by a paracrine mechanism. In our study, we used this analogue to determine whether endogenous pancreatic somatostatin has a role in the inhibition of glucagon secretion by hyperglycemia. The experiments were performed in pentobarbital-anesthetized, laparotomized dogs. To measure the pancreatic output of somatostatin directly, pancreatic venous blood was sampled from the right lobe of the dog pancreas, and the pancreatic blood flow was measured. In the first set of experiments, glucagon secretion was suppressed by a glucose infusion (200 mg/kg bolus and 20 mg .cntdot. kg-1 .cntdot. min-1 i.v.) for 3 h. Plasma glucose rose from 102 .+-. 6 to 365 .+-. 34 mg/dl. Pancreatic insulin output increased 10-fold, pancreatic somatostatin output increased from 1.2 .+-. 0.3 to 3.0 .+-. 0.8 ng/min, and pancreatic glucagon output was suppressed from 1.4 .+-. 0.7 to 0.5 .+-. 0.1 ng/min. After 2 h of glucose infusion, an infusion of the analogue (5.5 .mu.g/min i.v.) reversed both the stimulation of somatostatin and the suppression of glucagon without significantly changing either the plasma glucose level or the pancreatic insulin output. In a second set of experiments, basal somatostatin output was suppressed by the analogue (5.5 .mu.g/min i.v.) for 15 min before the administration of glucose. Pancreatic somatostatin output decreased from 2.6 .+-. 0.4 1.6 .+-. 0.3 ng/min, and pancreatic glucagon output rose from 1.2 .+-. 0.6 to 2.9 .+-. 0.9 ng/min. Glucose was then infused (200 mg/kg bolus and 20 mg .cntdot. kg-1 .cntdot. min-1 i.v.) in combination with the analogue. In response to glucose, somatostatin output rose, and glucagon output was suppressed back toward the original basal levels. Thus, in both sets of experiments, a reciprocal relationship between somatostatin and glucagon secretion was demonstrated regardless of whether the plasma glucose and insulin output changed. These data provide evidence that pancreatic somatostatin is a mediator of the suppression of glucagon during hyperglycemia.

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Accession: 006059502

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PMID: 2883057

DOI: 10.2337/diab.36.5.592

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