In the rat pancreas, somatostatin tonically inhibits glucagon secretion and is required for glucose-induced inhibition of glucagon secretion.
AIM
It is debated whether the inhibition of glucagon secretion by glucose results from direct effects of glucose on the α-cell (intrinsic regulation) or by paracrine effects exerted by beta- or delta-cell products.


METHODS
To study this in a more physiological model than isolated islets, we perfused isolated rat pancreases and measured glucagon, insulin and somatostatin secretion in response to graded increases in perfusate glucose concentration (from 3.5 to 4, 5, 6, 7, 8, 10, 12 mmol/L) as well as glucagon responses to blockage/activation of insulin/GABA/somatostatin signalling with or without addition of glucose.


RESULTS
Glucagon secretion was reduced by about 50% (compared to baseline secretion at 3.5 mmol/L) within minutes after increasing glucose from 4 to 5 mmol/L (P < .01, n = 13). Insulin secretion was increased minimally, but significantly, compared to baseline (3.5 mmol/L) at 4 mmol/L, whereas somatostatin secretion was not significantly increased from baseline until 7 mmol/L. Hereafter secretion of both increased gradually up to 12 mmol/L glucose. Neither recombinant insulin (1 µmol/L), GABA (300 µmol/L) or the insulin-receptor antagonist S961 (at 1 µmol/L) affected basal (3.5 mmol/L) or glucose-induced (5.0 mmol/L) attenuation of glucagon secretion (n = 7-8). Somatostatin-14 attenuated glucagon secretion by ~ 95%, and blockage of somatostatin-receptor (SSTR)-2 or combined blockage of SSTR-2, -3 and -5 by specific antagonists increased glucagon output (at 3.5 mmol/L glucose) and prevented glucose-induced (from 3.5 to 5.0 mmol/L) suppression of secretion.


CONCLUSION
Somatostatin is a powerful and tonic inhibitor of glucagon secretion from the rat pancreas and is required for glucose to inhibit glucagon secretion.
['Xu|Stella F S|SFS|', 'Andersen|Daniel B|DB|', 'Izarzugaza|Jose M G|JMG|0000-0003-1754-5122', 'Kuhre|Rune E|RE|0000-0003-4787-340X', 'Holst|Jens J|JJ|0000-0001-6853-3805']
D000818:Animals D005934:Glucagon D005947:Glucose D007328:Insulin D010179:Pancreas D010477:Perfusion D051381:Rats D013004:Somatostatin
somatostatin glucagon secretion intrinsic regulation insulin GABA isolated perfused rat pancreas paracrine regulation