胰高血糖素受体拮抗剂 MK-3577 可降低代谢健康的超重猫的胰高血糖素刺激血浆葡萄糖和胰岛素浓度。

IF 1.9 2区 农林科学 Q2 AGRICULTURE, DAIRY & ANIMAL SCIENCE
J Mott , C Celly , R Glock , C Gilor
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引用次数: 0

摘要

人们越来越认识到胰高血糖素紊乱在糖尿病中的作用,因此胰高血糖素拮抗剂可能有助于治疗高血糖和其他代谢紊乱。本研究旨在评估胰高血糖素受体拮抗剂 MK-3577 的药代动力学及其对健康猫血浆葡萄糖、胰岛素和胰高血糖素浓度的影响。在一项交叉安慰剂对照研究中,5 只专门饲养的猫分别接受了安慰剂、MK-3577(1 毫克/千克)或 MK-3577(3 毫克/千克)的治疗。分别在治疗后 0、15、225 和 240 分钟测量葡萄糖、胰岛素和胰高血糖素的浓度。胰高血糖素(20 微克/千克,IM)在 240 分钟时给药,葡萄糖和胰岛素在 255、265、275、285 和 300 分钟时测量。血浆中 MK-3577 的浓度分别在服用 1 毫克/千克和 3 毫克/千克后 4.2 小时和 3.2 小时达到峰值,半衰期分别为 14.8 小时和 15.5 小时。各治疗组的基线葡萄糖、胰岛素和胰高血糖素浓度没有显著差异。剂量为 3 毫克/千克时,MK-3577 可减弱胰高血糖素刺激的葡萄糖(p=0.0089)和胰岛素(p=0.02)的升高。剂量为 1 毫克/千克的 MK-3577 也有类似的趋势,但影响较小,且不显著。总之,GRA MK-3577 的药代动力学特征适合用于降低健康猫的胰高血糖素诱导的葡萄糖和胰岛素升高。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The glucagon-receptor antagonist MK-3577 reduces glucagon-stimulated plasma glucose and insulin concentrations in metabolically healthy overweight cats

The role of glucagon disturbances in diabetes mellitus is increasingly recognized and, hence, glucagon antagonism might aid in treatment of hyperglycemia and other metabolic disturbances. The aim of this study was to assess the pharmacokinetics of the glucagon receptor antagonist MK-3577 and its effect on plasma glucose, insulin, and glucagon concentrations in healthy cats. In a cross-over placebo-controlled study, 5 purpose-bred cats were treated with either Placebo, MK-3577 (1 mg/kg), or MK-3577 (3 mg/kg). Glucose, insulin and glucagon concentrations were measured at 0, 15, 225, 240 min post-treatment administration. Glucagon (20 mcg/kg, IM) was administered at 240 min and glucose and insulin were measured at 255, 265, 275, 285 and 300 min. Plasma MK-3577 concentrations peaked at 4.2 and 3.2 hours after 1 and 3 mg/kg dosing with a half-life of 14.8h and 15.5h respectively. Baseline glucose, insulin and glucagon concentrations did not differ significantly between treatment groups. At a dose of 3 mg/kg, MK-3577 blunted the glucagon-stimulated rise of glucose (p=0.0089) and insulin (p=0.02). Similar trends were observed with MK-3577 at the 1 mg/kg dose but the effect was smaller, and not significant. In conclusion, the GRA MK-3577 has a pharmacokinetic profile suitable for diminishing the glucagon-induced rise of glucose and insulin in healthy cats.

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来源期刊
Domestic animal endocrinology
Domestic animal endocrinology 农林科学-奶制品与动物科学
CiteScore
5.50
自引率
4.80%
发文量
58
审稿时长
31 days
期刊介绍: Domestic Animal Endocrinology publishes scientific papers dealing with the study of the endocrine physiology of domestic animal species. Those manuscripts utilizing other species as models for clinical or production problems associated with domestic animals are also welcome. Topics covered include: Classical and reproductive endocrinology- Clinical and applied endocrinology- Regulation of hormone secretion- Hormone action- Molecular biology- Cytokines- Growth factors
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