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<mods:namePart>Fernández Díaz, Cristina M. .</mods:namePart>
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<mods:namePart>Escobar Curbelo, Luis .</mods:namePart>
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<mods:namePart>López Acosta, J.F.</mods:namePart>
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<mods:namePart>Lobatón, Carmen D.</mods:namePart>
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<mods:namePart>Moreno, Alfredo</mods:namePart>
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<mods:namePart>Sanz Ortega, Julián</mods:namePart>
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<mods:namePart>Perdomo Hernández, Germán M.</mods:namePart>
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<mods:namePart>Cózar Castellano, Irene</mods:namePart>
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<mods:dateAccessioned encoding="iso8601">2018-11-02T10:09:38Z</mods:dateAccessioned>
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<mods:dateAvailable encoding="iso8601">2018-11-02T10:09:38Z</mods:dateAvailable>
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<mods:dateIssued encoding="iso8601">2018-11</mods:dateIssued>
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<mods:identifier type="issn">0213-3911</mods:identifier>
<mods:identifier type="uri">http://hdl.handle.net/10259/4994</mods:identifier>
<mods:identifier type="doi">10.14670/HH-11-997</mods:identifier>
<mods:abstract>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.</mods:abstract>
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<mods:languageTerm authority="rfc3066">eng</mods:languageTerm>
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<mods:accessCondition type="useAndReproduction">Attribution-NonCommercial-NoDerivatives 4.0 International</mods:accessCondition>
<mods:subject>
<mods:topic>Insulin-degrading enzyme</mods:topic>
</mods:subject>
<mods:subject>
<mods:topic>Type 2 diabetes,</mods:topic>
</mods:subject>
<mods:subject>
<mods:topic>Insulin treatment,</mods:topic>
</mods:subject>
<mods:subject>
<mods:topic>OHAs</mods:topic>
</mods:subject>
<mods:subject>
<mods:topic>Beta-cells</mods:topic>
</mods:subject>
<mods:subject>
<mods:topic>Alpha-cells</mods:topic>
</mods:subject>
<mods:subject>
<mods:topic>Rodent islets</mods:topic>
</mods:subject>
<mods:subject>
<mods:topic>Human islets</mods:topic>
</mods:subject>
<mods:titleInfo>
<mods:title>Insulin degrading enzyme is up-regulated in pancreatic β cells by insulin treatment</mods:title>
</mods:titleInfo>
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