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<field name="value">Fernández Díaz, Cristina M. .</field>
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<field name="value">Escobar Curbelo, Luis .</field>
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<field name="value">López Acosta, J.F.</field>
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<field name="value">Lobatón, Carmen D.</field>
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<field name="value">Moreno, Alfredo</field>
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<field name="value">Sanz Ortega, Julián</field>
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<field name="value">Perdomo Hernández, Germán M.</field>
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<field name="value">Cózar Castellano, Irene</field>
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<field name="value">2018-11-02T10:09:38Z</field>
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<field name="value">2018-11-02T10:09:38Z</field>
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<field name="value">2018-11</field>
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<field name="value">0213-3911</field>
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<field name="value">http://hdl.handle.net/10259/4994</field>
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<field name="value">10.14670/HH-11-997</field>
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<element name="en">
<field name="value">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.</field>
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<field name="value">Ministerio de&#xd;
Economia y Competitividad-Government of Spain and FEDER&#xd;
(SAF2014-58702-C2-1-R and SAF2014-58702-C2-2-R) to IC and to GP&#xd;
respectively.</field>
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<element name="es">
<field name="value">eng</field>
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<element name="publisher">
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<field name="value">Universidad de Murcia</field>
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<field name="value">Histology and Histopathology. 2018, V. 33, n. 11, p. 1167-1180</field>
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<field name="value">http://www.hh.um.es/2018/HH_33_11_2018.htm</field>
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<field name="value">info:eu-repo/grantAgreement/MINECO/SAF2014-58702-C2-1-R</field>
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<field name="value">Insulin-degrading enzyme</field>
<field name="value">Type 2 diabetes,</field>
<field name="value">Insulin treatment,</field>
<field name="value">OHAs</field>
<field name="value">Beta-cells</field>
<field name="value">Alpha-cells</field>
<field name="value">Rodent islets</field>
<field name="value">Human islets</field>
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<field name="value">Endocrinología</field>
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<element name="title">
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<field name="value">Insulin degrading enzyme is up-regulated in pancreatic β cells by insulin treatment</field>
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