Mechanisms involved in degradation of human insulin by cytosolic fractions of human, monkey, and rat liver - PubMed (original) (raw)
Mechanisms involved in degradation of human insulin by cytosolic fractions of human, monkey, and rat liver
V J Wroblewski et al. Diabetes. 1992 Apr.
Abstract
The degradation of native and 125I-labeled human insulin (HI) was examined in the cytosolic fraction of human, monkey, and rat liver. The purpose of these studies was to provide a species comparison of the interaction of insulin-degrading enzyme (IDE) and protein disulfide isomerase (PDI) in the degradation of HI. Western-blot analysis with monoclonal antibodies indicated the presence of both IDE and PDI in the cytosolic fraction of human and monkey liver. In contrast, rat liver cytosol contained, detectable levels of IDE only. A species comparison of metabolic profiles was performed by fractionating peptide products with reversed-phase high-performance liquid chromatography. After a 60-min incubation, human liver cytosol degraded unlabeled HI into three major products. Two of these peptides coeluted with the products of the incubation of HI with purified rat liver PDI. The three peptides were isolated and determined by NH2-terminal sequence analysis to be intact A chain, B chain, and des(Phe1)-B chain. Human liver cytosol also formed 125I-A chain and 125I-B chain as major products when specifically labeled 125I-HI isomers were used as substrate. Significant proteolytic degradation was observed only when reactions with human liver cytosol were supplemented with Mn2+. In contrast, monkey and rat liver cytosol proteolytically degraded 125I-HI isomers to small peptide fragments. The rat and monkey metabolic profiles were similar to each other and to that observed with Mn(2+)-supplemented human liver cytosol. Proteolysis in monkey and rat was sensitive to inhibition by EDTA.(ABSTRACT TRUNCATED AT 250 WORDS)
Similar articles
- Demonstration of specific insulin binding to cytosolic proteins in H35 hepatoma cells, rat liver and skeletal muscle.
Harada S, Smith RM, Smith JA, Shah N, Jarett L. Harada S, et al. Biochem J. 1995 Feb 15;306 ( Pt 1)(Pt 1):21-8. doi: 10.1042/bj3060021. Biochem J. 1995. PMID: 7864812 Free PMC article. - [125I]-insulin metabolism by the rat liver in vivo: evidence that a neutral thiol-protease mediates rapid intracellular insulin degradation.
Williams FG, Johnson DE, Bauer GE. Williams FG, et al. Metabolism. 1990 Mar;39(3):231-41. doi: 10.1016/0026-0495(90)90041-a. Metabolism. 1990. PMID: 2407925 - Endosomal proteolysis of insulin by an acidic thiol metalloprotease unrelated to insulin degrading enzyme.
Authier F, Rachubinski RA, Posner BI, Bergeron JJ. Authier F, et al. J Biol Chem. 1994 Jan 28;269(4):3010-6. J Biol Chem. 1994. PMID: 8300632 - Insulin degradation: progress and potential.
Duckworth WC, Bennett RG, Hamel FG. Duckworth WC, et al. Endocr Rev. 1998 Oct;19(5):608-24. doi: 10.1210/edrv.19.5.0349. Endocr Rev. 1998. PMID: 9793760 Review. - Insulin degradation: mechanisms, products, and significance.
Duckworth WC. Duckworth WC. Endocr Rev. 1988 Aug;9(3):319-45. doi: 10.1210/edrv-9-3-319. Endocr Rev. 1988. PMID: 3061785 Review.
Cited by
- The regulation of Hypoxia-Inducible Factor-1 (HIF-1alpha) expression by Protein Disulfide Isomerase (PDI).
Kobayashi Y, Oguro A, Hirata Y, Imaoka S. Kobayashi Y, et al. PLoS One. 2021 Feb 4;16(2):e0246531. doi: 10.1371/journal.pone.0246531. eCollection 2021. PLoS One. 2021. PMID: 33539422 Free PMC article. - Protein disulphide-isomerase reduces ricin to its A and B chains in the endoplasmic reticulum.
Spooner RA, Watson PD, Marsden CJ, Smith DC, Moore KA, Cook JP, Lord JM, Roberts LM. Spooner RA, et al. Biochem J. 2004 Oct 15;383(Pt 2):285-93. doi: 10.1042/BJ20040742. Biochem J. 2004. PMID: 15225124 Free PMC article. - The role of s-nitrosylation and s-glutathionylation of protein disulphide isomerase in protein misfolding and neurodegeneration.
Halloran M, Parakh S, Atkin JD. Halloran M, et al. Int J Cell Biol. 2013;2013:797914. doi: 10.1155/2013/797914. Epub 2013 Nov 18. Int J Cell Biol. 2013. PMID: 24348565 Free PMC article. Review. - The Basis for Weekly Insulin Therapy: Evolving Evidence With Insulin Icodec and Insulin Efsitora Alfa.
Rosenstock J, Juneja R, Beals JM, Moyers JS, Ilag L, McCrimmon RJ. Rosenstock J, et al. Endocr Rev. 2024 May 7;45(3):379-413. doi: 10.1210/endrev/bnad037. Endocr Rev. 2024. PMID: 38224978 Free PMC article. Review. - Protein disulfide isomerase A1 as a novel redox sensor in VEGFR2 signaling and angiogenesis.
Nagarkoti S, Kim YM, Ash D, Das A, Vitriol E, Read TA, Youn SW, Sudhahar V, McMenamin M, Hou Y, Boatwright H, Caldwell R, Essex DW, Cho J, Fukai T, Ushio-Fukai M. Nagarkoti S, et al. Angiogenesis. 2023 Feb;26(1):77-96. doi: 10.1007/s10456-022-09852-7. Epub 2022 Aug 19. Angiogenesis. 2023. PMID: 35984546 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical