TY - JOUR
T1 - Adrenoceptor antagonists, but not guanethidine, reduce glucopenia-induced glucagon secretion from perfused rat pancreas
AU - Ito, Katsuhiko
AU - Hirose, Hiroshi
AU - Kido, Koichi
AU - Koyama, Kazunori
AU - Maruyama, Hiroshi
AU - Saruta, Takao
N1 - Funding Information:
The authors thank Roger H. Unger, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, for critical review of the manuscript. We also thank Takashi Mamizuka, Shuji Oguchi and Eiko Takeshita (Clinical Laboratories, Keio University School of Medicine) for technical assistance with the radioimmunoassay and HPLC. This work was supported in part by a grant-in-aid for scientific research from the Ministry of Education, Science and Culture, Japan, and by grants to KI and HH from Keio University School of Medicine, Tokyo, Japan. Part of this work was presented at the 54th Annual Meeting and Scientific Sessions of the American Diabetes Association in New Orleans, on June 14, 1994.
PY - 1995/12
Y1 - 1995/12
N2 - This study was designed to investigate (1) whether norepinephrine is released in response to glucopenia in vitro, thereby stimulating glucagon secretion and, (2) the modulating effects of norepinephrine on insulin and glucagon secretion, using isolated perfused rat pancreas preparations. Simultaneous addition of the adrenergic receptor antagonists yohimbine, prazosin and propranolol, each at a concentration of 10-5 mol/l, significantly potentiated glucose-stimulated insulin secretion (6.23 ± 0.76 vs. 2.11 ± 0.72 (control) nmol/min, P < 0.01), and suppressed glucopenia-induced glucagon secretion (0.59 ± 0.10 vs. 1.34 ± 0.18 (control) ng/min, P < 0.05). Also, 10-5 mol/l yohimbine alone significantly potentiated glucose-stimulated insulin secretion (4.86 ± 0.50 nmol/min, P < 0.05). The norepinephrine release inhibitor, guanethidine, significantly inhibited tyramine-induced secretion of both norepinephrine (7.86 ± 0.77 vs. 49.7 ± 2.3 nmol/min, P < 0.01) and glucagon (0.31 ± 0.08 vs. 1.21 ± 0.15 ng/min, P < 0.01), but exerted no effects on glucopenia-induced secretion of either norepinephrine or glucagon. We conclude that these results further support the concept that the neurotransmitter norepinephrine is released in response to glucopenia in vitro, and modulates insulin and glucagon secretion. Our data do not, however, provide evidence indicating that glucopenia-induced glucagon secretion is mainly mediated by activation of sympathetic nerve terminals around the α-cells in the isolated perfused rat pancreas.
AB - This study was designed to investigate (1) whether norepinephrine is released in response to glucopenia in vitro, thereby stimulating glucagon secretion and, (2) the modulating effects of norepinephrine on insulin and glucagon secretion, using isolated perfused rat pancreas preparations. Simultaneous addition of the adrenergic receptor antagonists yohimbine, prazosin and propranolol, each at a concentration of 10-5 mol/l, significantly potentiated glucose-stimulated insulin secretion (6.23 ± 0.76 vs. 2.11 ± 0.72 (control) nmol/min, P < 0.01), and suppressed glucopenia-induced glucagon secretion (0.59 ± 0.10 vs. 1.34 ± 0.18 (control) ng/min, P < 0.05). Also, 10-5 mol/l yohimbine alone significantly potentiated glucose-stimulated insulin secretion (4.86 ± 0.50 nmol/min, P < 0.05). The norepinephrine release inhibitor, guanethidine, significantly inhibited tyramine-induced secretion of both norepinephrine (7.86 ± 0.77 vs. 49.7 ± 2.3 nmol/min, P < 0.01) and glucagon (0.31 ± 0.08 vs. 1.21 ± 0.15 ng/min, P < 0.01), but exerted no effects on glucopenia-induced secretion of either norepinephrine or glucagon. We conclude that these results further support the concept that the neurotransmitter norepinephrine is released in response to glucopenia in vitro, and modulates insulin and glucagon secretion. Our data do not, however, provide evidence indicating that glucopenia-induced glucagon secretion is mainly mediated by activation of sympathetic nerve terminals around the α-cells in the isolated perfused rat pancreas.
KW - Glucagon
KW - Insulin
KW - Norepinephrine
KW - Perfused rat pancreas
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U2 - 10.1016/0168-8227(95)01189-7
DO - 10.1016/0168-8227(95)01189-7
M3 - Article
C2 - 8861456
AN - SCOPUS:0029549597
SN - 0168-8227
VL - 30
SP - 173
EP - 180
JO - Diabetes Research and Clinical Practice
JF - Diabetes Research and Clinical Practice
IS - 3
ER -
