Antibody-Mediated Inhibition of Insulin-Degrading Enzyme Improves Insulin Activity in a Diabetic Mouse Model.
ScFv library
antibody
antibody engineering
diabetes
insulin-degrading enzyme (IDE)
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
14
12
2021
accepted:
26
01
2022
entrez:
30
3
2022
pubmed:
31
3
2022
medline:
9
4
2022
Statut:
epublish
Résumé
Diabetes is a metabolic disease that may lead to different life-threatening complications. While insulin constitutes a beneficial treatment, its use may be limited due to increased degradation and an increase in side effects such as weight gain and hypoglycemia. Small molecule inhibitors to insulin-degrading enzyme (IDE) have been previously suggested as a potential treatment for diabetes through their ability to reduce insulin degradation and thus increase insulin activity. Nevertheless, their tendency to bind to the zinc ion in the catalytic site of IDE may affect other important metalloproteases and limit their clinical use. Here, we describe the isolation of an IDE-specific antibody that specifically inhibits insulin degradation by IDE. Using phage display, we generated a human IDE-specific antibody that binds human and mouse IDE with high affinity and specificity and can differentiate between active IDE to a mutated IDE with reduced catalytic activity in the range of 30 nM. We further assessed the ability of that IDE-inhibiting antibody to improve insulin activity
Identifiants
pubmed: 35350789
doi: 10.3389/fimmu.2022.835774
pmc: PMC8958001
doi:
Substances chimiques
Antibodies
0
Insulin
0
Insulysin
EC 3.4.24.56
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
835774Informations de copyright
Copyright © 2022 Fursht, Liran, Nash, Medala, Ini, Royal, Goldsmith, Nahary, Benhar and Frenkel.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Nature. 2006 Oct 19;443(7113):870-4
pubmed: 17051221
Am J Med. 1987 Jun;82(6):1247-52
pubmed: 3300307
South Med J. 1990 Aug;83(8):904-11
pubmed: 2382156
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4162-7
pubmed: 12634421
Clin Cornerstone. 2006;8 Suppl 2:S19-26
pubmed: 16939874
Eur J Immunol. 1988 Feb;18(2):313-6
pubmed: 3350037
Diabetes Care. 1984 Mar-Apr;7(2):188-99
pubmed: 6376015
Diabetologia. 2009 Aug;52(8):1656-64
pubmed: 19396426
Protein Eng. 1994 Dec;7(12):1509-15
pubmed: 7716163
Diabetes. 2003 Jun;52(6):1562-7
pubmed: 12765971
Diabetes. 1974 Jun;23(6):536-43
pubmed: 4834293
Important Adv Oncol. 1990;:3-18
pubmed: 2182522
Nat Commun. 2015 Sep 23;6:8250
pubmed: 26394692
FASEB J. 2021 May;35(5):e21374
pubmed: 33835493
Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5153-8
pubmed: 24706856
J Mol Biol. 2010 Jan 15;395(2):430-43
pubmed: 19896952
J Biol Chem. 1993 Oct 15;268(29):21538-44
pubmed: 8104941
Cell Cycle. 2015;14(14):2293-300
pubmed: 25945652
Lancet. 2005 Nov 12;366(9498):1736-43
pubmed: 16291068
Nat Rev Drug Discov. 2016 Nov;15(11):786-804
pubmed: 27516169
J Med Chem. 2018 Sep 27;61(18):8174-8185
pubmed: 30148634
Hum Mol Genet. 2000 Sep 1;9(14):2149-58
pubmed: 10958757
Endocrine. 2021 Feb;71(2):357-364
pubmed: 33398768
J Biol Chem. 2002 Mar 15;277(11):9437-46
pubmed: 11779865
Trends Endocrinol Metab. 2016 Jan;27(1):24-34
pubmed: 26651592
J Biol Chem. 2013 Jan 25;288(4):2281-9
pubmed: 23188819
Nat Rev Drug Discov. 2003 Jan;2(1):52-62
pubmed: 12509759
Methods Mol Biol. 2019;1904:455-480
pubmed: 30539486
Nature. 2014 Jul 3;511(7507):94-8
pubmed: 24847884
N Engl J Med. 1986 Jul 24;315(4):252-4
pubmed: 3724817
Am J Med. 2009 May;122(5):443-53
pubmed: 19375554
J Biol Chem. 1990 Sep 5;265(25):14828-35
pubmed: 2203763
J Biol Chem. 2011 Jul 1;286(26):22711-5
pubmed: 21576244
MAbs. 2009 May-Jun;1(3):281-7
pubmed: 20065645
Diabetes. 2014 Jul;63(7):2232-43
pubmed: 24931034
J Pharm Sci. 2001 Jan;90(1):1-11
pubmed: 11064373
MedGenMed. 2004 Aug 24;6(3 Suppl):12
pubmed: 15647717
Vitam Horm. 2009;80:635-48
pubmed: 19251053
Anal Biochem. 1992 Sep;205(2):263-70
pubmed: 1332541
Endocr Rev. 1998 Oct;19(5):608-24
pubmed: 9793760
Trends Pharmacol Sci. 2002 Apr;23(4):177-83
pubmed: 11931993
PLoS One. 2011;6(6):e20818
pubmed: 21695259
Diabet Med. 1998 Jul;15(7):539-53
pubmed: 9686693
Annu Rev Biomed Eng. 2000;2:339-76
pubmed: 11701516
Curr Pharm Des. 2009;15(31):3644-55
pubmed: 19925417
ACS Infect Dis. 2021 Aug 13;7(8):2362-2369
pubmed: 33876632
Nat Methods. 2009 May;6(5):343-5
pubmed: 19363495
Biomedicines. 2021 Jan 17;9(1):
pubmed: 33477364
J Mol Biol. 2004 Jan 2;335(1):177-92
pubmed: 14659749
Lancet. 2012 Jun 16;379(9833):2291-9
pubmed: 22683129
PLoS One. 2010 May 07;5(5):e10504
pubmed: 20498699