Ribeiro-Oliveira Antônio, Schweizer Junia R O L, Amaral Pedro H S, Bizzi Mariana F, Silveira Warley Cezar da, Espirito-Santo Daniel T A, Zille Giancarlo, Soares Beatriz S, Schmid Herbert A, Yuen Kevin C J
a Department of Internal Medicine, Laboratory of Endocrinology, School of Medicine , Federal University of Minas Gerais , Belo Horizonte , MG , Brazil.
b Department of Oncology Research , Novartis Institutes for BioMedical Research, Novartis Pharma AG , Basel , Switzerland.
Stress. 2018 Jul;21(4):370-375. doi: 10.1080/10253890.2018.1451838. Epub 2018 Apr 17.
Pasireotide is a new-generation somatostatin analog that acts through binding to multiple somatostatin receptor subtypes. Studies have shown that pasireotide induces hyperglycemia, reduces glucocorticoid secretion, alters neurotransmission, and potentially affects stress responses typically manifested as hyperglycemia and increased corticosterone secretion. This study specifically aimed to evaluate whether pasireotide treatment modifies glucose and costicosterone secretion in response to acute restraint stress. Male Holtzman rats of 150-200 g were treated with pasireotide (10 µg/kg/day) twice-daily for two weeks or vehicle for the same period. Blood samples were collected at baseline and after 5, 10, 30, and 60 min of restraint stress. The three experimental groups comprised of vehicle + restraint (VEHR), pasireotide + restraint (PASR), and pasireotide + saline (PASNR). Following pasireotide treatment, no significant differences in baseline glucose and corticosterone levels were observed among the three groups. During restraint, hyperglycemia was observed at 10 min (p < .01 for both comparisons), peaked at 30 min (p < .01 for both comparisons) and showed higher 60 min areas under glucose curves in the VEHR and PASR stressed groups when compared to the non-stressed PASNR group (p < .05 for both comparisons). Restraint also increased corticosterone secretion in the VEHR and PASR stressed groups at 5 min (p < .01 for both comparisons), and peaked at 30 min (p < .01 for both comparisons) with corresponding higher 60 min areas under corticosterone curves when compared to the non-stressed PASNR group (p < .01 for both comparisons). In conclusion, pasireotide treatment does not modify hyperglycemic- and corticosterone-restraint stress responses, thus preserving acute stress regulation.
帕西瑞肽是一种新一代生长抑素类似物，通过与多种生长抑素受体亚型结合发挥作用。研究表明，帕西瑞肽可诱发高血糖、减少糖皮质激素分泌、改变神经传递，并可能影响通常表现为高血糖和皮质酮分泌增加的应激反应。本研究的具体目的是评估帕西瑞肽治疗是否会改变急性束缚应激下的血糖和皮质酮分泌。150 - 200克的雄性霍尔兹曼大鼠每天接受两次帕西瑞肽（10微克/千克/天）治疗，持续两周，同期接受赋形剂治疗。在基线以及束缚应激5、10、30和60分钟后采集血样。三个实验组分别为赋形剂 + 束缚（VEHR）、帕西瑞肽 + 束缚（PASR）和帕西瑞肽 + 生理盐水（PASNR）。帕西瑞肽治疗后，三组之间的基线血糖和皮质酮水平未观察到显著差异。在束缚期间，10分钟时观察到高血糖（两次比较均p < 0.01），30分钟时达到峰值（两次比较均p < 0.01），与非应激的PASNR组相比，VEHR和PASR应激组在60分钟时血糖曲线下面积更高（两次比较均p < 0.05）。束缚还使VEHR和PASR应激组在5分钟时皮质酮分泌增加（两次比较均p < 0.01），30分钟时达到峰值（两次比较均p < 0.01），与非应激的PASNR组相比，相应的60分钟时皮质酮曲线下面积更高（两次比较均p < 0.01）。总之，帕西瑞肽治疗不会改变高血糖和皮质酮束缚应激反应，从而保留急性应激调节功能。
