Insulin degradation products from perfused rat kidney
The kidney is a major site for insulin metabolism, but the enzymes involved and the products generated have not been established. To examine the products, we have perfused rat kidneys with insulin specifically iodinated on either the A14 or the B26 tyrosine. Labeled material from both the perfusate and kidney extract was examined by Sephadex G50 and high-performance liquid chromatography (HPLC). In perfusate from a filtering kidney, 22% of the insulin-sized material was not intact insulin on HPLC. With the nonfiltering kidney, 10.6% was not intact insulin. Labeled material from HPLC was sulfitolyzed and reinjected on HPLC. By use of /sup 125/I-iodo(A14)-insulin, almost all the degradation products contained an intact A-chain. By use of /sup 125/I-iodo(B26)-insulin, several different B-chain-cleaved products were obtained. The material extracted from the perfused kidney was different from perfusate products but similar to intracellular products from hepatocytes, suggesting that cellular metabolism by kidney and liver are similar. The major intracellular product had characteristics consistent with a cleavage between the B16 and B17 amino acids. This product and several of the perfusate products are also produced by insulin protease suggesting that this enzyme is involved in the degradation of insulin by kidney.
- Research Organization:
- Veterans Administration Medical Center, Omaha, NE (USA)
- OSTI ID:
- 6279227
- Journal Information:
- Am. J. Physiol.; (United States), Vol. 256
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
INSULIN
METABOLISM
IN VITRO
IODINE 125
ISOTOPE DILUTION
KIDNEYS
LIQUID COLUMN CHROMATOGRAPHY
PEPTIDE HYDROLASES
PERFUSED ORGANS
RATS
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
HORMONES
HYDROLASES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
ORGANS
PEPTIDE HORMONES
RADIOISOTOPES
RODENTS
SEPARATION PROCESSES
TRACER TECHNIQUES
VERTEBRATES
550501* - Metabolism- Tracer Techniques