Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme
Insulin-degrading enzyme (IDE) is a highly conserved and ubiquitously expressed metalloprotease that degrades insulin and several other intermediate-size peptides. For many decades, IDE had been assumed to be involved primarily in hepatic insulin clearance, a key process that regulates availability...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/1/86 |
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| author | Carlos M. González-Casimiro Beatriz Merino Elena Casanueva-Álvarez Tamara Postigo-Casado Patricia Cámara-Torres Cristina M. Fernández-Díaz Malcolm A. Leissring Irene Cózar-Castellano Germán Perdomo |
| author_facet | Carlos M. González-Casimiro Beatriz Merino Elena Casanueva-Álvarez Tamara Postigo-Casado Patricia Cámara-Torres Cristina M. Fernández-Díaz Malcolm A. Leissring Irene Cózar-Castellano Germán Perdomo |
| author_sort | Carlos M. González-Casimiro |
| collection | DOAJ |
| description | Insulin-degrading enzyme (IDE) is a highly conserved and ubiquitously expressed metalloprotease that degrades insulin and several other intermediate-size peptides. For many decades, IDE had been assumed to be involved primarily in hepatic insulin clearance, a key process that regulates availability of circulating insulin levels for peripheral tissues. Emerging evidence, however, suggests that IDE has several other important physiological functions relevant to glucose and insulin homeostasis, including the regulation of insulin secretion from pancreatic β-cells. Investigation of mice with tissue-specific genetic deletion of <i>Ide</i> in the liver and pancreatic β-cells (L-IDE-KO and B-IDE-KO mice, respectively) has revealed additional roles for IDE in the regulation of hepatic insulin action and sensitivity. In this review, we discuss current knowledge about IDE’s function as a regulator of insulin secretion and hepatic insulin sensitivity, both evaluating the classical view of IDE as an insulin protease and also exploring evidence for several non-proteolytic functions. Insulin proteostasis and insulin sensitivity have both been highlighted as targets controlling blood sugar levels in type 2 diabetes, so a clearer understanding the physiological functions of IDE in pancreas and liver could led to the development of novel therapeutics for the treatment of this disease. |
| first_indexed | 2024-03-09T04:31:31Z |
| format | Article |
| id | doaj.art-22708589f9ef4a9e8032286530c55b73 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T04:31:31Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-22708589f9ef4a9e8032286530c55b732023-12-03T13:34:45ZengMDPI AGBiomedicines2227-90592021-01-01918610.3390/biomedicines9010086Modulation of Insulin Sensitivity by Insulin-Degrading EnzymeCarlos M. González-Casimiro0Beatriz Merino1Elena Casanueva-Álvarez2Tamara Postigo-Casado3Patricia Cámara-Torres4Cristina M. Fernández-Díaz5Malcolm A. Leissring6Irene Cózar-Castellano7Germán Perdomo8Instituto de Biología y Genética Molecular, University of Valladolid-CSIC, 47003 Valladolid, SpainInstituto de Biología y Genética Molecular, University of Valladolid-CSIC, 47003 Valladolid, SpainInstituto de Biología y Genética Molecular, University of Valladolid-CSIC, 47003 Valladolid, SpainInstituto de Biología y Genética Molecular, University of Valladolid-CSIC, 47003 Valladolid, SpainInstituto de Biología y Genética Molecular, University of Valladolid-CSIC, 47003 Valladolid, SpainMolecular Oncology Group, IMDEA Food Institute, CEI UAM + CSIC, 28049 Madrid, SpainInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine (UCI MIND), Irvine, CA 92697, USAInstituto de Biología y Genética Molecular, University of Valladolid-CSIC, 47003 Valladolid, SpainInstituto de Biología y Genética Molecular, University of Valladolid-CSIC, 47003 Valladolid, SpainInsulin-degrading enzyme (IDE) is a highly conserved and ubiquitously expressed metalloprotease that degrades insulin and several other intermediate-size peptides. For many decades, IDE had been assumed to be involved primarily in hepatic insulin clearance, a key process that regulates availability of circulating insulin levels for peripheral tissues. Emerging evidence, however, suggests that IDE has several other important physiological functions relevant to glucose and insulin homeostasis, including the regulation of insulin secretion from pancreatic β-cells. Investigation of mice with tissue-specific genetic deletion of <i>Ide</i> in the liver and pancreatic β-cells (L-IDE-KO and B-IDE-KO mice, respectively) has revealed additional roles for IDE in the regulation of hepatic insulin action and sensitivity. In this review, we discuss current knowledge about IDE’s function as a regulator of insulin secretion and hepatic insulin sensitivity, both evaluating the classical view of IDE as an insulin protease and also exploring evidence for several non-proteolytic functions. Insulin proteostasis and insulin sensitivity have both been highlighted as targets controlling blood sugar levels in type 2 diabetes, so a clearer understanding the physiological functions of IDE in pancreas and liver could led to the development of novel therapeutics for the treatment of this disease.https://www.mdpi.com/2227-9059/9/1/86insulin-degrading enzymeinsulin resistancepancreasliverinsulin receptorglucose transporters |
| spellingShingle | Carlos M. González-Casimiro Beatriz Merino Elena Casanueva-Álvarez Tamara Postigo-Casado Patricia Cámara-Torres Cristina M. Fernández-Díaz Malcolm A. Leissring Irene Cózar-Castellano Germán Perdomo Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme Biomedicines insulin-degrading enzyme insulin resistance pancreas liver insulin receptor glucose transporters |
| title | Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme |
| title_full | Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme |
| title_fullStr | Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme |
| title_full_unstemmed | Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme |
| title_short | Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme |
| title_sort | modulation of insulin sensitivity by insulin degrading enzyme |
| topic | insulin-degrading enzyme insulin resistance pancreas liver insulin receptor glucose transporters |
| url | https://www.mdpi.com/2227-9059/9/1/86 |
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