RT info:eu-repo/semantics/article T1 Targeting insulin-degrading enzyme in insulin clearance A1 Leissring, Malcolm A. A1 González Casimiro, Carlos Manuel A1 Merino Antolín, Beatriz A1 Suire, Caitlin N. A1 Perdomo Hernández, Germán K1 Insulin K1 Insulina K1 Diabetes K1 Insulin resistance K1 Liver K1 Liver - Diseases K1 Hígado - Enfermedades K1 Enzyme inhibitors K1 Enzimas K1 Hepatología K1 Pharmacology K1 Insulin-degrading enzyme K1 32 Ciencias Médicas K1 2415 Biología Molecular AB Hepatic insulin clearance, a physiological process that in response to nutritional cues clears ~50–80% of circulating insulin, is emerging as an important factor in our understanding of the pathogenesis of type 2 diabetes mellitus (T2DM). Insulin-degrading enzyme (IDE) is a highly conserved Zn2+-metalloprotease that degrades insulin and several other intermediate-size peptides. Both, insulin clearance and IDE activity are reduced in diabetic patients, albeit the cause-effect relationship in humans remains unproven. Because historically IDE has been proposed as the main enzyme involved in insulin degradation, efforts in the development of IDE inhibitors as therapeutics in diabetic patients has attracted attention during the last decades. In this review, we retrace the path from Mirsky’s seminal discovery of IDE to the present, highlighting the pros and cons of the development of IDE inhibitors as a pharmacological approach to treating diabetic patients. PB MDPI SN 1422-0067 YR 2021 FD 2021 LK https://uvadoc.uva.es/handle/10324/59963 UL https://uvadoc.uva.es/handle/10324/59963 LA eng NO International Journal of Molecular Sciences, 2021, Vol. 22, Nº. 5, 2235 NO Producción Científica DS UVaDOC RD 03-jun-2024