RT info:eu-repo/semantics/article
T1 Insulin degrading enzyme is up-regulated in pancreatic β cells by insulin treatment
A1 Fernández Díaz, Cristina M. .
A1 Escobar Curbelo, Luis .
A1 López Acosta, J.F.
A1 Lobatón, Carmen D.
A1 Moreno, Alfredo
A1 Sanz Ortega, Julián
A1 Perdomo Hernández, Germán M.
A1 Cózar Castellano, Irene
K1 Insulin-degrading enzyme
K1 Type 2 diabetes,
K1 Insulin treatment,
K1 OHAs
K1 Beta-cells
K1 Alpha-cells
K1 Rodent islets
K1 Human islets
K1 Endocrinología
K1 Endocrinology
AB Insulin Degrading Enzyme (IDE) is anendopeptidase that degrades insulin and glucagon. Idegene has been associated with type-2 diabetes mellitus(DM2). However, the physiological role(s) of IDE inglucose homeostasis and its potential therapeutic benefitremain not completely known.To contribute in the understanding of IDE's role inglucose metabolism, we analyzed IDE protein level inpancreatic islets from two hyperinsulinemic mousemodels, db/db and high-fat diet (HFD) mice, as well asin human islets from DM2 patients treated with oralhypoglycemic agents (OHAs) or insulin. IDE proteinlevel was detected by staining and by western-blot.INS1E cells, rat and human islets were treated withinsulin and IDE protein level was studied.We have shown for the first time IDE staining inrodent and human tissue, using the proper negativecontrol, IDE null mouse tissue. Our staining indicatesthat IDE is expressed in both beta- and alpha-cells, withhigher expression in alpha-cells. Db/db and HFD miceislets showed increased IDE protein level. Interestingly,human islets from DM2 patients treated with OHAsshowed decreased IDE protein level in beta-cells.Meanwhile, islets from insulin-treated DM2 patientsshowed augmented IDE protein level compared toOHAs patients, pointing to an upregulation of IDEprotein level stimulated by insulin. These data correlatenicely with insulin-stimulated upregulation of IDE incultured INS1E cells, as well as in rat and human islets.In conclusion, our study shows that IDE is expressedin pancreatic beta- and alpha-cells of both rodents andhumans, having higher expression in alpha-cells.Furthermore, insulin stimulates IDE protein level inpancreatic beta-cells. These results may haveimplications in how DM2 patient’s treatment affectstheir beta-cell function.
PB Universidad de Murcia
SN 0213-3911
YR 2018
FD 2018-11
LK http://hdl.handle.net/10259/4994
UL http://hdl.handle.net/10259/4994
LA eng
NO Ministerio deEconomia y Competitividad-Government of Spain and FEDER(SAF2014-58702-C2-1-R and SAF2014-58702-C2-2-R) to IC and to GPrespectively.
DS Repositorio Institucional de la Universidad de Burgos
RD 11-dic-2024