Por favor, use este identificador para citar o enlazar este ítem:https://uvadoc.uva.es/handle/10324/61166
Título
Pharmacological activation of insulin‐degrading enzyme improves insulin secretion and glucose tolerance in diet‐induced obese mice
Autor
Año del Documento
2023
Editorial
Wiley
Descripción
Producción Científica
Documento Fuente
Diabetes, Obesity and Metabolism, 2023.
Resumo
Aim:To investigate the use of synthetic preimplantation factor (sPIF) as a potentialtherapeutic tool for improving glucose-stimulated insulin secretion (GSIS), glucose tol-erance and insulin sensitivity in the setting of diabetes.Materials and Methods:We used a preclinical murine model of type 2 diabetes(T2D) induced by high-fat diet (HFD) feeding for 12 weeks. Saline or sPIF (1 mg/kg/day) was administered to mice by subcutaneously implanted osmotic mini-pumps for25 days. Glucose tolerance, circulating insulin and C-peptide levels, and GSIS wereassessed. In addition,β-cells (Min-6) were used to test the effects of sPIF on GSISand insulin-degrading enzyme (IDE) activity in vitro. The effect of sPIF on GSIS wasalso tested in human islets.Results:GSIS was enhanced 2-fold by sPIF in human islets ex vivo. Furthermore, con-tinuous administration of sPIF to HFD mice increased circulating levels of insulin andimproved glucose tolerance, independently of hepatic insulin clearance. Of note,islets isolated from mice treated with sPIF exhibited restoredβ-cell function. Finally,genetic (shRNA-IDE) or pharmacological (6bK) inactivation of IDE in Min-6 abolished
Materias Unesco
23 Química
2302 Bioquímica
Palabras Clave
Antidiabetic drug
Insulin
Insulina
Glucose
Glucosa
ISSN
1462-8902
Revisión por pares
SI
Patrocinador
“la Caixa”Foundation (Grant/Award Number:LCF/PR/PR18/51130007)
Ministerio de Ciencia y Universidades (PID2019-110496RB-C21 y PID2019-110496RB-C22)
Generalitat de Catalunya (2017SGR1439)
CIBERBBN - financiado por el Instituto de Salud Carlos III (ISCIII) y FEDER (CB06-01-0074)
Junta de Castilla y León (Programa Estratégico del Instituto de Biología y Genética Molecular (IBGM)) (Ref. CLU-2019-02)
Junta de Castilla y León y el Fondo Social Europeo (ORDERDU/1508/2020)
Ministerio de Ciencia y Universidades (PID2019-110496RB-C21 y PID2019-110496RB-C22)
Generalitat de Catalunya (2017SGR1439)
CIBERBBN - financiado por el Instituto de Salud Carlos III (ISCIII) y FEDER (CB06-01-0074)
Junta de Castilla y León (Programa Estratégico del Instituto de Biología y Genética Molecular (IBGM)) (Ref. CLU-2019-02)
Junta de Castilla y León y el Fondo Social Europeo (ORDERDU/1508/2020)
Version del Editor
Propietario de los Derechos
© 2023 The Author(s)
Idioma
eng
Tipo de versión
info:eu-repo/semantics/publishedVersion
Derechos
openAccess
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