Nakamura R, Hayashi M, Emmanouel D S, Katz A I
Am J Physiol. 1986 Jan;250(1 Pt 2):F144-50. doi: 10.1152/ajprenal.1986.250.1.F144.
Uptake and degradation of peptide hormones have been demonstrated in proximal convoluted tubules (PCT), but the contribution of other regions of the nephron to renal hormone metabolism is unknown. In the present study we used micromethods to determine for the first time the degradation of radiolabeled insulin and glucagon by each segment of the rabbit nephron and examined some characteristics of this process in proximal convoluted and cortical collecting tubules (CCT). Degradation of insulin (8-10 fmol . cm-1 . h-1) and glucagon (13-15 fmol . cm-1 . h-1) was maximal in proximal convoluted and straight tubules, but occurred to a substantial degree (approximately 25-30% of PCT) in all other segments of the nephron except the thin descending limb. In PCT degradation of both hormones was maximal at physiological pH, and competition studies suggested that it is brought about by both specific and nonspecific proteases. Most of the degrading activity (insulin, 86%; glucagon, 73%) was in the cytosol or could be eluted off the cell membrane or organelles. In the CCT, a representative segment of the distal nephron, the characteristics of insulin degradation were similar to those observed in the PCT, whereas glucagon degradation appeared to be due chiefly to nonspecific proteases. In conclusion, the metabolism of insulin and glucagon by isolated rabbit tubules occurs chiefly in the proximal convoluted and straight tubules, but up to one-third of the degrading capacity of the proximal nephron is also present in distal nephron segments.(ABSTRACT TRUNCATED AT 250 WORDS)
肽类激素的摄取和降解已在近端曲管（PCT）中得到证实，但肾单位其他区域对肾激素代谢的作用尚不清楚。在本研究中，我们首次使用微量方法来测定兔肾单位各节段对放射性标记胰岛素和胰高血糖素的降解，并研究了近端曲管和皮质集合管（CCT）中这一过程的一些特征。胰岛素（8 - 10 fmol·cm⁻¹·h⁻¹）和胰高血糖素（13 - 15 fmol·cm⁻¹·h⁻¹）的降解在近端曲管和直小管中最大，但在肾单位除细降支外的所有其他节段中也有相当程度的降解（约为PCT的25 - 30%）。在PCT中，两种激素的降解在生理pH值时最大，竞争研究表明这是由特异性和非特异性蛋白酶共同引起的。大多数降解活性（胰岛素为86%；胰高血糖素为73%）存在于胞质溶胶中，或可从细胞膜或细胞器上洗脱下来。在远端肾单位的代表性节段CCT中，胰岛素降解的特征与在PCT中观察到的相似，而胰高血糖素的降解似乎主要是由非特异性蛋白酶引起的。总之，分离的兔肾小管对胰岛素和胰高血糖素的代谢主要发生在近端曲管和直小管中，但近端肾单位高达三分之一的降解能力也存在于远端肾单位节段中。（摘要截短于250字）
