Pituitary adenylate cyclase-activating polypeptide stimulates insulin and glucagon secretion in humans

Pituitary adenylate cyclase-activating polypeptide stimulates insulin and glucagon secretion in humans
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DOI:
10.1210/jc.82.9.3093
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发表时间:
1997-09-01
影响因子:
5.8
通讯作者:
Ahren, B
Ahren, B
中科院分区:
医学2区
文献类型:
--
作者:
Filipsson, K;Tornoe, K;Ahren, B

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垂体腺苷酸环化酶激活多肽(PACAP)已经定位于胰腺神经,并在实验动物中被证明可以刺激胰岛素和胰高血糖素的分泌。本研究探讨了PACAP在人体胰腺中的发生及其可能的功能。提取的人胰腺组织中PACAP27和PACAP38的含量分别为0.44 +/- 0.04 pmol/g和29.6 +/- 6.4 pmol/g。此外,在7名年龄均为57岁的健康绝经后妇女的同质组中,静脉输注合成人PACAP27 (3 pmol/kg min,持续75 min)可增加胰岛素、C肽和胰高血糖素的基础水平,但在14 min后对基础血糖没有显著影响。15min时,快速给药葡萄糖(0.3 g/kg,静脉注射)。PACAP27输注时,葡萄糖灌注后胰岛素峰值为797 +/- 232 pmol/L。生理盐水输注时559 +/- 164 pmol/L (P = 0.018)。PACAP27可增强葡萄糖后C肽的峰值(P = 0.018)。相比之下,以C肽/胰岛素摩尔比计算的肝脏提取量没有受到PACAP27的显著影响,PACAP27也没有改变葡萄糖消除率和葡萄糖诱导峰后血清胰岛素的降低。我们得出结论,PACAP发生在人体胰腺中,刺激人体胰岛素和胰高血糖素的分泌。这表明PACAP参与了人类胰岛功能的调节。
Pituitary adenylate cyclase-activating polypeptide (PACAP) has been localized to pancreatic nerves and demonstrated to stimulate insulin and glucagon secretion in experimental animals. This study examined the occurrence and possible function of PACAP in the human pancreas. The content of PACAP27 was 0.44 +/- 0.04 pmol/g tissue, and that of PACAP38 was 29.6 +/- 6.4 pmol/g tissue in extracted human pancreas (n = 4). Furthermore, in a homogeneous group of seven healthy postmenopausal women, all aged 57 yr, iv infusion of synthetic human PACAP27 (3 pmol/kg min for 75 min) increased basal levels of insulin, C peptide, and glucagon without significantly influencing basal glucose after 14 min. At 15 min, glucose was administered rapidly (0.3 g/kg, iv). The peak insulin after bolus glucose was 797 +/- 232 pmol/L during PACAP27 infusion us. 559 +/- 164 pmol/L during saline infusion (P = 0.018). Also, the peak in C peptide after glucose was potentiated by PACAP27 (P = 0.018). rn contrast, hepatic extraction, calculated as the C peptide/insulin molar ratio, was not significantly affected by PACAP27, and neither the glucose elimination rate nor reduction of serum insulin after the glucose-induced peak was changed by PACAP27. We conclude that PACAP occurs in human pancreas and stimulates insulin and glucagon secretion in humans. This suggests that PACAP is involved in the regulation of islet function in humans.