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<dc:creator>Fernández Díaz, Cristina M. .</dc:creator>
<dc:creator>Escobar Curbelo, Luis .</dc:creator>
<dc:creator>López Acosta, J.F.</dc:creator>
<dc:creator>Lobatón, Carmen D.</dc:creator>
<dc:creator>Moreno, Alfredo</dc:creator>
<dc:creator>Sanz Ortega, Julián</dc:creator>
<dc:creator>Perdomo Hernández, Germán M.</dc:creator>
<dc:creator>Cózar Castellano, Irene</dc:creator>
<dc:date>2018-11</dc:date>
<dc:description>Insulin Degrading Enzyme (IDE) is an&#xd;
endopeptidase that degrades insulin and glucagon. Ide&#xd;
gene has been associated with type-2 diabetes mellitus&#xd;
(DM2). However, the physiological role(s) of IDE in&#xd;
glucose homeostasis and its potential therapeutic benefit&#xd;
remain not completely known.&#xd;
To contribute in the understanding of IDE's role in&#xd;
glucose metabolism, we analyzed IDE protein level in&#xd;
pancreatic islets from two hyperinsulinemic mouse&#xd;
models, db/db and high-fat diet (HFD) mice, as well as&#xd;
in human islets from DM2 patients treated with oral&#xd;
hypoglycemic agents (OHAs) or insulin. IDE protein&#xd;
level was detected by staining and by western-blot.&#xd;
INS1E cells, rat and human islets were treated with&#xd;
insulin and IDE protein level was studied.&#xd;
We have shown for the first time IDE staining in&#xd;
rodent and human tissue, using the proper negative&#xd;
control, IDE null mouse tissue. Our staining indicates&#xd;
that IDE is expressed in both beta- and alpha-cells, with&#xd;
higher expression in alpha-cells. Db/db and HFD mice&#xd;
islets showed increased IDE protein level. Interestingly,&#xd;
human islets from DM2 patients treated with OHAs&#xd;
showed decreased IDE protein level in beta-cells.&#xd;
Meanwhile, islets from insulin-treated DM2 patients&#xd;
showed augmented IDE protein level compared to&#xd;
OHAs patients, pointing to an upregulation of IDE&#xd;
protein level stimulated by insulin. These data correlate&#xd;
nicely with insulin-stimulated upregulation of IDE in&#xd;
cultured INS1E cells, as well as in rat and human islets.In conclusion, our study shows that IDE is expressed&#xd;
in pancreatic beta- and alpha-cells of both rodents and&#xd;
humans, having higher expression in alpha-cells.&#xd;
Furthermore, insulin stimulates IDE protein level in&#xd;
pancreatic beta-cells. These results may have&#xd;
implications in how DM2 patient’s treatment affects&#xd;
their beta-cell function.</dc:description>
<dc:format>application/pdf</dc:format>
<dc:identifier>http://hdl.handle.net/10259/4994</dc:identifier>
<dc:language>eng</dc:language>
<dc:publisher>Universidad de Murcia</dc:publisher>
<dc:title>Insulin degrading enzyme is up-regulated in pancreatic β cells by insulin treatment</dc:title>
<dc:type>info:eu-repo/semantics/article</dc:type>
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