EurekaMag.com logo
+ Site Statistics
References:
53,214,146
Abstracts:
29,074,682
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

Pancreatic somatostatin is a mediator of glucagon inhibition by hyperglycemia


Diabetes 36(5): 592-596
Pancreatic somatostatin is a mediator of glucagon inhibition by hyperglycemia
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.

(PDF same-day service: $19.90)

Accession: 006059502

PMID: 2883057

DOI: 10.2337/diab.36.5.592



Related references

The effect of the intra pancreatic calcium and glucagon administration on the somatostatin induced inhibition of insulin and glucagon secretion in dogs. Folia Endocrinologica Japonica 55(3): 201-209, 1979

Effect of hyperglycemia and hyperglycemia plus somatostatin on plasma glucagon in human obesity. Diabetologia 30(7): 560A-561A, 1987

Inhibition of pancreatic glucagon release by somatostatin: in vitro. Scandinavian Journal of Clinical and Laboratory Investigation 33(2): 125-129, 1974

Phentolamine prevents the somatostatin-mediated inhibition of pancreatic glucagon secretion. Metabolism: Clinical and Experimental 26(8): 841-845, 1977

Effects of insulin, glucagon, and somatostatin on the release of somatostatin-25 and somatostatin-14 from rainbow trout, Oncorhynchus mykiss, pancreatic islets in vitro. General and Comparative Endocrinology 99(2): 211-220, 1995

Somatostatin inhibition of pancreatic glucagon release from monolayer cultures and interactions with calcium. Endocrinology 101(3): 911-919, 1977

Inhibition of gastrin glucagon and serotonin hypersecretion dependent on pancreatic apudomas by somatostatin 14. Revista Espanola de las Enfermedades del Aparato Digestivo 72(4): 329-333, 1987

Inhibition of pancreatic apudoma-dependent hypersecretion of gastrin, glucagon and serotonin using somatostatin-14. Revista Espanola de Las Enfermedades del Aparato Digestivo 72(4 Pt 1): 329-333, 1987

Inhibition of pancreatic glucagon responses to arginine by somatostatin in normal man and in insulin-dependent diabetics. Diabetes 23(11): 876-880, 1974

Specific inhibition of rat pancreatic insulin or glucagon release by receptor-selective somatostatin analogs. Biochemical and Biophysical Research Communications 205(1): 341-346, 1994