Receptor-mediated endocytosis of A14-125I-insulin by the nonfiltering perfused rat kidney

Hitoshi Sato, Kuniaki Yoshioka, Tetsuya Terasaki, Akira Tsuji

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

The mechanism of insulin uptake and/or degradation in the peritubular circulation of the kidney was investigated using nonfiltering perfused rat kidneys, in which glomerular filtration was sufficiently reduced. After perfusion of A14-125I-insulin in the nonfiltering kidney for designated intervals, the acid-wash technique was employed to separately measure the acid-extractable and acid-resistant A14-125I-insulin, which were quantitated by HPLC and TCA-precipitability. HPLC profiles showed that the nonfiltering kidney metabolizes A14-125I-insulin only to a small extent during 1-h perfusion, suggesting that the peritubular clearance of A14-125I-insulin was not due to extracellular degradation but for the most part to uptake by the kidney. Acid-extractable A14-125I-insulin rapidly increased with time and reached pseudo-equilibrium with perfusate at approx. 10 min, whereas acid-resistant A14-125I-insulin increased continuously. An endocytosis inhibitor, phenylarsine oxide, inhibited significantly the acid-resistant A14-125I-insulin with no change in acid-extractable A14-125I-insulin, suggesting that the peritubular uptake of A14-125I-insulin largely represents endocytosis of the peptide into the intracellular space. Moreover, both the acid-extractable and acid-resistant A14-125I-insulin were significantly decreased in the presence of unlabeled insulin (1 μM). These lines of evidence suggest that insulin is taken up by the nonfiltering perfused kidney via receptor-mediated endocytosis (RME), which possibly occurs at the basolateral side of renal tubular cells, and that the peritubular clearance of insulin is largely accounted for by this mechanism.

Original languageEnglish
Pages (from-to)442-450
Number of pages9
JournalBBA - General Subjects
Volume1073
Issue number3
DOIs
Publication statusPublished - 1991 Apr 9
Externally publishedYes

Keywords

  • (Rat)
  • Basolateral endocytosis
  • Insulin receptor
  • Nonfiltering perfused kidney
  • Peritubular clearance

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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