RT info:eu-repo/semantics/article
T1 Pharmacological activation of insulin‐degrading enzyme improves insulin secretion and glucose tolerance in diet‐induced obese mice
A1 Sanz González, Alba
A1 Cózar Castellano, Irene
A1 Broca, Christophe
A1 Sabatier, Julia
A1 Acosta Crespo, Gerardo A.
A1 Royo, Miriam
A1 Hernándo Muñoz, Carla
A1 Torroba, Tomás
A1 Perdomo Hernández, Germán
A1 Merino Antolín, Beatriz
K1 Antidiabetic drug
K1 Insulin
K1 Insulina
K1 Glucose
K1 Glucosa
K1 23 Química
K1 2302 Bioquímica
AB 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
PB Wiley
SN 1462-8902
YR 2023
FD 2023
LK https://uvadoc.uva.es/handle/10324/61166
UL https://uvadoc.uva.es/handle/10324/61166
LA eng
NO Diabetes, Obesity and Metabolism, 2023.
NO Producción Científica
DS UVaDOC
RD 06-ago-2024