Differences in renal metabolism of insulin and cytochrome c

Journal Article · Fri Apr 01 04:00:00 EST 1988 · American Journal of Physiology; (USA)

OSTI ID:7014872

Herrman, J; Simmons, R E; Frank, B H; Rabkin, R ^[1]

---

1. Stanford Univ., CA (USA) Veterans Administration Medical Center, Palo Alto (USA) Lilly Research Labs., Indianapolis, IN (USA)

Kidneys degrade small proteins such as cytochrome c (CYT c) by the classic lysosomal pathway. However, because alternate routes for the transport and degradation of protein hormones have been identified in other tissues, the authors set out to determine whether extralysosomal sites might participate in the renal degradation of insulin. First, they compared the effect of the lysosomal inhibitor NH{sub 4}Cl on insulin and CYT c degradation by isolated perfused rat kidneys. After kidneys were loaded with radiolabeled proteins to allow for absorption and transport to lysosomes, degradation was measured in the presence or absence of inhibitors. Next they followed the subcellular distribution of {sup 125}I-labeled insulin in kidneys exposed to {sup 125}I-labeled insulin in vivo or when isolated and perfused. Under both circumstances the distribution of insulin on a linear sucrose gradient differed from that of the lysosomal enzyme N-acetyl-{beta}-glucosaminidase. In contrast, ({sup 14}CH{sub 3})CYT c, injected in vivo, distributed over a density similar to the lysosomal marker. Thus important differences exist between the renal metabolism of CYT c, which proceeds in lysosomes, and the renal metabolism of insulin. These include rate of degradation, sensitivity to NH{sub 4}Cl, and subcellular sites of localization. Accordingly, they suggest that insulin degradation may occur, at least in part, in a different compartment from the classic lysosomal site of protein degradation.

• OSTI ID: 7014872
• Journal Information: American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 254:4; ISSN 0002-9513; ISSN AJPHA
• Country of Publication: United States
• Language: English

Related Subjects

551001* -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMMONIUM CHLORIDES
AMMONIUM COMPOUNDS
AMMONIUM HALIDES
ANIMAL TISSUES
BETA DECAY RADIOISOTOPES
BIODEGRADATION
BIOLOGICAL PATHWAYS
BODY
CARBON 14 COMPOUNDS
CELL CONSTITUENTS
CHEMICAL REACTIONS
CHLORIDES
CHLORINE COMPOUNDS
CYTOCHROMES
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
ELECTRON CAPTURE RADIOISOTOPES
HALIDES
HALOGEN COMPOUNDS
HORMONES
INSULIN
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KIDNEYS
LABELLED COMPOUNDS
LYSOSOMES
METABOLISM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
PEPTIDE HORMONES
PERFUSED TISSUES
PIGMENTS
PROTEINS
RADIOISOTOPES
TISSUES
TRACER TECHNIQUES