Drosophila insulin degrading enzyme and rat skeletal muscle insulin protease cleave insulin at similar sites

Journal Article · Tue Mar 21 04:00:00 EST 1989 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00432a018· OSTI ID:5673188

Duckworth, W C; Garcia, J V; Liepnieks, J J; Hamel, F G; Hermodson, M A; Frank, B H; Rosner, M R ^[1]

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1. Veterans Administration Medical Center, Omaha, NE (USA)

Insulin degradation is an integral part of the cellular action of insulin. Recent evidence suggests that the enzyme insulin protease is involved in the degradation of insulin in mammalian tissues. Drosophila, which has insulin-like hormones and insulin receptor homologues, also expresses an insulin degrading enzyme with properties that are very similar to those of mammalian insulin protease. In the present study, the insulin cleavage products generated by the Drosophila insulin degrading enzyme were identified and compared with the products generated by the mammalian insulin protease. Both purified enzymes were incubated with porcine insulin specifically labeled with {sup 125}I on either the A19 or B26 position, and the degradation products were analyzed by HPLC before and after sulfitolysis. Isolation and sequencing of the cleavage products indicated that both enzymes cleave the A chain of intact insulin at identical sites between residues A13 and A14 and A14 and A15. These results demonstrate that all the insulin cleavage sites generated by the Drosopohila insulin degrading enzyme are shared in common with the mammalian insulin protease. These data support the hypothesis that there is evolutionary conservation of the insulin degrading enzyme and further suggest that this enzyme plays an important role in cellular function.

• OSTI ID: 5673188
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 28:6; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ARTHROPODS
BETA DECAY RADIOISOTOPES
BIODEGRADATION
BIOLOGICAL EVOLUTION
CHEMICAL REACTIONS
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
DIPTERA
DROSOPHILA
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
FLIES
FRUIT FLIES
HORMONES
HYDROLASES
INSECTS
INSULIN
INTERMEDIATE MASS NUCLEI
INVERTEBRATES
IODINE 125
IODINE ISOTOPES
ISOTOPES
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MUSCLES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PEPTIDE HYDROLASES
PEPTIDES
PROTEINS
RADIOISOTOPES
RATS
RODENTS
SEPARATION PROCESSES
VERTEBRATES