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In the rat pancreas, somatostatin tonically inhibits glucagon secretion and is required for glucose‐induced inhibition of glucagon secretion
Author(s) -
Xu Stella F. S.,
Andersen Daniel B.,
Izarzugaza Jose M. G.,
Kuhre Rune E.,
Holst Jens J.
Publication year - 2020
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.13464
Subject(s) - medicine , endocrinology , glucagon , somatostatin , insulin , secretion , l glucose , chemistry , biology , islet
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.