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犬体内胰多肽的代谢以肾脏为主,无肝脏代谢。

Predominance of renal and absence of hepatic metabolism of pancreatic polypeptide in the dog.

作者信息

Hagopian W, Lever E G, Cohen D, Emmanouel D, Polonsky K S, Pugh W, Moossa A, Jaspan J B

出版信息

Am J Physiol. 1983 Aug;245(2):E171-7. doi: 10.1152/ajpendo.1983.245.2.E171.

DOI:10.1152/ajpendo.1983.245.2.E171
PMID:6881330
Abstract

Pancreatic polypeptide (PP) metabolism was studied in the dog. Metabolic clearance rate (MCR) of PP was found to be 9.5 +/- 0.9 ml . kg-1 . min-1, accounted for predominantly by renal extraction (34.9 +/- 2.6% of exogenous PP), which comprised 45.5 +/- 5.8% of total PP clearance. Hepatic extraction of both endogenous (-9.9 +/- 6.1%) and exogenous (2.2 +/- 1.4%) PP infused to pharmacological levels was negligible, as was its splanchnic extraction (4.2 +/- 0.9%). Renal organ clearance of exogenous PP (3.7 +/- 0.3 ml . kg-1 . min-1) closely approximated that of inulin (3.6 +/- 0.3 ml . kg-1 . min-1), indicating that renal PP metabolism occurs entirely by glomerular filtration without contribution from peritubular uptake mechanisms. Urinary PP, chromatographically indistinguishable from that in plasma but quantitatively accounting for less than 1% of overall renal PP uptake, indicated virtually complete renal degradation of the peptide to nonimmunoreactive fragments. Renal PP extraction was shown to be nonsaturable. Plasma half disappearance time of PP was 10.1 +/- 1.0 min and apparent distribution space 307 +/- 39 ml/kg. Linkage between the hepatic action and degradation of insulin and glucagon has been proposed, and in this light absent hepatic PP extraction is noteworthy. This finding, reminiscent of the hepatic handling of metabolically inert C-peptide and biologically inactive glucagon peptides, is consistent with the absence of demonstrable physiological function of PP.

摘要

对狗的胰多肽(PP)代谢进行了研究。发现PP的代谢清除率(MCR)为9.5±0.9 ml·kg⁻¹·min⁻¹,主要由肾脏摄取所致(占外源性PP的34.9±2.6%),这占PP总清除率的45.5±5.8%。注入药理水平的内源性PP(-9.9±6.1%)和外源性PP(2.2±1.4%)的肝脏摄取可忽略不计,其内脏摄取(4.2±0.9%)也是如此。外源性PP的肾脏器官清除率(3.7±0.3 ml·kg⁻¹·min⁻¹)与菊粉的清除率(3.6±0.3 ml·kg⁻¹·min⁻¹)非常接近,表明肾脏PP代谢完全通过肾小球滤过发生,而肾小管周围摄取机制没有作用。尿PP在色谱上与血浆中的无法区分,但在数量上占肾脏PP总摄取量的不到1%,表明该肽在肾脏中几乎完全降解为无免疫反应性的片段。肾脏PP摄取显示为非饱和性。PP的血浆半衰期为10.1±1.0分钟,表观分布容积为307±39 ml/kg。有人提出胰岛素和胰高血糖素的肝脏作用与降解之间存在联系,鉴于此,肝脏缺乏PP摄取值得注意。这一发现让人想起肝脏对代谢惰性C肽和生物无活性胰高血糖素肽的处理,与PP缺乏可证实的生理功能一致。

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