EFFECTS OF ALPHA-2-ADRENERGIC AND BETA-ADRENERGIC AGONISM ON GLUCAGON-SECRETION FROM PERFUSED PANCREASES OF NORMAL AND STREPTOZOCIN-INDUCED DIABETIC RATS
EFFECTS OF ALPHA-2-ADRENERGIC AND BETA-ADRENERGIC AGONISM ON GLUCAGON-SECRETION FROM PERFUSED PANCREASES OF NORMAL AND STREPTOZOCIN-INDUCED DIABETIC RATS
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DOI：
10.1016/0026-0495(93)90025-j
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发表时间：
1993-08-01
影响因子：
9.8
通讯作者：
SARUTA, T
中科院分区：
文献类型：
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作者：
HIROSE, H;MARUYAMA, H;SARUTA, T
在实验动物和人体中，已知胰岛素分泌受α2-肾上腺素能激动剂抑制，受β-肾上腺素能激动剂刺激。相比之下，肾上腺素对胰高血糖素分泌的调节仍然存在争议。本研究采用正常和链脲佐菌素诱导的糖尿病（STZ-D）大鼠离体胰腺灌流，观察α2-和β-肾上腺素能激动剂对胰岛α细胞的影响。α2肾上腺素受体激动剂可乐定在10− 7 mol/L浓度下显著刺激正常大鼠（1，286 ± 90 v417 ± 53 ng/L，P< .01）和STZ-D大鼠（551 ± 86 v130 ± 19 ng/L，P< .01）的胰高血糖素分泌。此外，与正常大鼠（751 ± 130 v347 ± 41 ng/L，P<0.05）和STZ-D大鼠（182 ± 22 v92 ± 20 ng/L，P<0.01）的基础水平相比，10− 7 mol/L的β-肾上腺素受体激动剂异丙肾上腺素显著刺激胰高血糖素分泌。此外，这些α2-和β-激动作用在α2-肾上腺素受体拮抗剂育亨宾存在时几乎完全被抑制，β-激动作用在浓度为10− 6 mol/L时几乎与普萘洛尔相同。STZ-D大鼠胰岛素分泌明显减少。这些结果表明，即使在严重的糖尿病状态下，不仅β-肾上腺素能激动剂，而且α2-肾上腺素能激动剂也刺激大鼠胰腺α细胞分泌胰高血糖素。
Insulin secretion is known to be inhibited by α2-adrenergic agonism and stimulated by β-adrenergic agonism in both experimental animals and humans. In contrast, adrenergic regulation of glucagon secretion remains controversial. This study was designed to determine the effects of α2- and β-adrenergic agonism on islet α cells, using isolated perfused pancreata of normal and streptozocin-induced diabetic (STZ-D) rats. The α2-adrenoceptor agonist clonidine at a concentration of 10−7mol/L significantly stimulated glucagon secretion as compared with basal levels in both normal (1,286 ± 90v417 ± 53 ng/L,P< .01) and STZ-D rats (551 ± 86v130 ± 19 ng/L,P< .01). Also, the β-adrenoceptor agonist isoproterenol at a concentration of 10−7mol/L significantly stimulated glucagon secretion as compared with basal levels in both normal (751 ± 130v347 ± 41 ng/L,P< .05) and STZ-D rats (182 ± 22v92 ± 20 ng/L,P< .01). Furthermore, these α2- and β-agonistic effects were almost completely inhibited in the presence of the α2-adrenoceptor antagonist yohimbine and the β-agonistic effects were almost propranolol at a concentration of 10−6mol/L, respectively. Insulin secretion was markedly reduced in STZ-D rats. These results suggest that even in a severely diabetic state, not only β- but also α2-adrenergic agonism stimulates glucagon secretion from rat pancreatic α cells.