Insulin degradation products from perfused rat kidney

W. C. Duckworth, F. G. Hamel, J. Liepnieks, D. Peavy, B. Frank, R. Rabkin

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 125I-iodo (A14)-insulin, almost all the degradation products contained an intact A-chain. By use of 125I-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.

Original languageEnglish (US)
Pages (from-to)19/2
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume256
Issue number2
StatePublished - Jan 1 1989

Fingerprint

Rats
Insulin
Kidney
Degradation
High performance liquid chromatography
High Pressure Liquid Chromatography
Metabolism
Insulysin
Enzymes
Liver
Tyrosine
Hepatocytes
Amino Acids

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Duckworth, W. C., Hamel, F. G., Liepnieks, J., Peavy, D., Frank, B., & Rabkin, R. (1989). Insulin degradation products from perfused rat kidney. American Journal of Physiology - Endocrinology and Metabolism, 256(2), 19/2.

Insulin degradation products from perfused rat kidney. / Duckworth, W. C.; Hamel, F. G.; Liepnieks, J.; Peavy, D.; Frank, B.; Rabkin, R.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 256, No. 2, 01.01.1989, p. 19/2.

Research output: Contribution to journalArticle

Duckworth, WC, Hamel, FG, Liepnieks, J, Peavy, D, Frank, B & Rabkin, R 1989, 'Insulin degradation products from perfused rat kidney', American Journal of Physiology - Endocrinology and Metabolism, vol. 256, no. 2, pp. 19/2.
Duckworth, W. C. ; Hamel, F. G. ; Liepnieks, J. ; Peavy, D. ; Frank, B. ; Rabkin, R. / Insulin degradation products from perfused rat kidney. In: American Journal of Physiology - Endocrinology and Metabolism. 1989 ; Vol. 256, No. 2. pp. 19/2.
@article{412080e5a5f045acbaf06c4f3c3c83d2,
title = "Insulin degradation products from perfused rat kidney",
abstract = "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 125I-iodo (A14)-insulin, almost all the degradation products contained an intact A-chain. By use of 125I-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.",
author = "Duckworth, {W. C.} and Hamel, {F. G.} and J. Liepnieks and D. Peavy and B. Frank and R. Rabkin",
year = "1989",
month = "1",
day = "1",
language = "English (US)",
volume = "256",
pages = "19/2",
journal = "American Journal of Physiology - Renal Physiology",
issn = "0363-6127",
publisher = "American Physiological Society",
number = "2",

}

TY - JOUR

T1 - Insulin degradation products from perfused rat kidney

AU - Duckworth, W. C.

AU - Hamel, F. G.

AU - Liepnieks, J.

AU - Peavy, D.

AU - Frank, B.

AU - Rabkin, R.

PY - 1989/1/1

Y1 - 1989/1/1

N2 - 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 125I-iodo (A14)-insulin, almost all the degradation products contained an intact A-chain. By use of 125I-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.

AB - 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 125I-iodo (A14)-insulin, almost all the degradation products contained an intact A-chain. By use of 125I-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.

UR - http://www.scopus.com/inward/record.url?scp=0024542621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024542621&partnerID=8YFLogxK

M3 - Article

C2 - 2645781

AN - SCOPUS:0024542621

VL - 256

SP - 19/2

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 0363-6127

IS - 2

ER -