The Role of Proteases and Serpin Protease Inhibitors in β-Cell Biology and Diabetes.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101596414 Publication Model: Electronic Cited Medium: Internet ISSN: 2218-273X (Electronic) Linking ISSN: 2218273X NLM ISO Abbreviation: Biomolecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, 2011-

Signal Transduction*; Diabetes Mellitus/*metabolism ; Serpins/*metabolism; Animals ; Diabetes Mellitus/genetics ; Humans ; Peptide Hydrolases/genetics ; Peptide Hydrolases/metabolism ; Serpins/classification ; Serpins/genetics

Regulation of the equilibrium between proteases and their inhibitors is fundamental to health maintenance. Consequently, developing a means of targeting protease activity to promote tissue regeneration and inhibit inflammation may offer a new strategy in therapy development for diabetes and other diseases. Specifically, recent efforts have focused on serine protease inhibitors, known as serpins, as potential therapeutic targets. The serpin protein family comprises a broad range of protease inhibitors, which are categorized into 16 clades that are all extracellular, with the exception of Clade B, which controls mostly intracellular proteases, including both serine- and papain-like cysteine proteases. This review discusses the most salient, and sometimes opposing, views that either inhibition or augmentation of protease activity can bring about positive outcomes in pancreatic islet biology and inflammation. These potential discrepancies can be reconciled at the molecular level as specific proteases and serpins regulate distinct signaling pathways, thereby playing equally distinct roles in health and disease development.

Cell Death Differ. 2010 Apr;17(4):586-95. (PMID: 19893573)
Acta Endocrinol (Copenh). 1967 Jul;55(3):537-44. (PMID: 4166389)
J Autoimmun. 2010 Mar;34(2):96-104. (PMID: 19664906)
Int J Mol Sci. 2019 Nov 29;20(23):. (PMID: 31795482)
Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5635-9. (PMID: 1376927)
Science. 1998 Apr 17;280(5362):450-3. (PMID: 9545226)
Pediatr Diabetes. 2016 Aug;17(5):351-9. (PMID: 26073583)
Chem Rev. 2002 Dec;102(12):4751-804. (PMID: 12475206)
Cancer Res. 2005 Dec 15;65(24):11501-9. (PMID: 16357159)
J Histochem Cytochem. 2002 Nov;50(11):1443-54. (PMID: 12417609)
Eur J Clin Invest. 1983 Jun;13(3):231-5. (PMID: 6191995)
BMJ Open Diabetes Res Care. 2016 Nov 24;4(1):e000274. (PMID: 27933185)
Front Endocrinol (Lausanne). 2020 Jul 30;11:450. (PMID: 32903749)
J Biol Chem. 1995 Dec 15;270(50):29854-61. (PMID: 8530382)
Biol Open. 2021 Jun 15;10(6):. (PMID: 34125181)
J Mol Biol. 1999 Oct 15;293(1):29-39. (PMID: 10512713)
J Clin Invest. 2005 Oct;115(10):2934-43. (PMID: 16184198)
Diabetes Res Clin Pract. 1988 Oct 14;5(4):249-55. (PMID: 3266137)
J Clin Endocrinol Metab. 2014 Aug;99(8):E1418-26. (PMID: 24527714)
Diabetologia. 2019 May;62(5):822-834. (PMID: 30824970)
Int J Mol Sci. 2021 Jun 14;22(12):. (PMID: 34198511)
J Immunol. 2012 Jun 15;188(12):6319-27. (PMID: 22593614)
Hum Gene Ther. 2006 Jun;17(6):625-34. (PMID: 16776571)
Diabetologia. 2002 May;45(5):686-92. (PMID: 12107749)
Immunology. 2014 Oct 13;:. (PMID: 25308894)
J Biol Chem. 1998 Jan 23;273(4):1851-4. (PMID: 9442015)
Adv Enzyme Regul. 2004;44:309-20. (PMID: 15581498)
Prion. 2007 Jan-Mar;1(1):15-20. (PMID: 19164889)
Immunol Cell Biol. 1999 Feb;77(1):47-57. (PMID: 10101686)
Sci Transl Med. 2021 Apr 7;13(588):. (PMID: 33827974)
Indian J Med Res. 2013 Nov;138(5):591-4. (PMID: 24434314)
Diabetes. 2021 Feb;70(2):492-503. (PMID: 33277337)
J Biol Chem. 2013 Jan 18;288(3):1612-9. (PMID: 23195956)
Nature. 1985 Oct 24-30;317(6039):730-2. (PMID: 3877243)
Gene Ther. 2004 Jan;11(2):181-6. (PMID: 14712302)
Cell Mol Life Sci. 2004 Feb;61(3):301-25. (PMID: 14770295)
J Biol Chem. 2001 Sep 7;276(36):33293-6. (PMID: 11435447)
J Autoimmun. 2015 Dec;65:56-63. (PMID: 26343333)
Diabet Med. 2009 Dec;26(12):1309-10. (PMID: 20002490)
Am J Respir Cell Mol Biol. 1998 May;18(5):670-4. (PMID: 9569237)
Pancreas. 2009 May;38(4):461-7. (PMID: 19188865)
Nature. 1992 Jun 18;357(6379):605-7. (PMID: 1608473)
Nat Immunol. 2012 Feb 26;13(4):361-8. (PMID: 22366893)
Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16236-41. (PMID: 18852465)
Immunol Lett. 2013 Feb;150(1-2):61-8. (PMID: 23333354)
Exp Biol Med (Maywood). 2012 Jul;237(7):793-802. (PMID: 22829702)
Nat Struct Biol. 1996 Aug;3(8):676-81. (PMID: 8756325)
Diabetes. 1997 Aug;46(8):1296-304. (PMID: 9231654)
Clin Rev Allergy Immunol. 2013 Oct;45(2):267-80. (PMID: 23325331)
J Biol Chem. 2016 Jan 1;291(1):266-78. (PMID: 26578518)
Cell Metab. 2016 Jan 12;23(1):194-205. (PMID: 26701651)
Biochemistry. 2003 Jun 24;42(24):7381-9. (PMID: 12809493)
PLoS One. 2010 Sep 22;5(9):e12894. (PMID: 20877570)
Nephrol Dial Transplant. 1996 Jun;11(6):987-9. (PMID: 8671957)
Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12319-24. (PMID: 18713856)
J Exp Med. 2007 Aug 6;204(8):1901-9. (PMID: 17664292)
Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12153-8. (PMID: 16093309)
Respir Med. 2011 Aug;105(8):1129-39. (PMID: 21367592)
IUBMB Life. 2002 Jul;54(1):1-7. (PMID: 12387568)
Immunobiology. 2002 Sep;205(4-5):542-51. (PMID: 12396014)
Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16242-7. (PMID: 18852471)
Clin Dev Immunol. 2013;2013:986789. (PMID: 24454481)
Diabetes. 2013 Feb;62(2):531-42. (PMID: 23139348)
J Autoimmun. 1999 May;12(3):191-8. (PMID: 10222028)
Genome Biol. 2006;7(5):216. (PMID: 16737556)
Thromb Haemost. 1980 Dec 19;44(3):130-4. (PMID: 6162208)
Cell Mol Life Sci. 2008 Aug;65(16):2541-53. (PMID: 18516497)
Lab Invest. 1986 Nov;55(5):551-6. (PMID: 2430139)
J Clin Invest. 1991 May;87(5):1819-27. (PMID: 1708786)
Diabetes Res Clin Pract. 1992 Oct;18(1):35-42. (PMID: 1280191)
Diabetes. 2007 May;56(5):1316-23. (PMID: 17360983)
Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):15443-8. (PMID: 22949661)

DK108739-01A1 National Institute of Health

Keywords: diabetes; pancreatic islet; protease; serpin

0 (Serpins)
EC 3.4.- (Peptide Hydrolases)

Date Created: 20220121 Date Completed: 20220329 Latest Revision: 20220329

20221213

PMC8774208

10.3390/biom12010067

35053215