Histology and Histopathology. 2018, V. 33, n. 11, p. 1167-1180
Universidad de Murcia
Fecha de publicación :
Insulin Degrading Enzyme (IDE) is an
endopeptidase that degrades insulin and glucagon. Ide
gene has been associated with type-2 diabetes mellitus
(DM2). However, the physiological role(s) of IDE in
glucose homeostasis and its potential therapeutic benefit
remain not completely known.
To contribute in the understanding of IDE's role in
glucose metabolism, we analyzed IDE protein level in
pancreatic islets from two hyperinsulinemic mouse
models, db/db and high-fat diet (HFD) mice, as well as
in human islets from DM2 patients treated with oral
hypoglycemic agents (OHAs) or insulin. IDE protein
level was detected by staining and by western-blot.
INS1E cells, rat and human islets were treated with
insulin and IDE protein level was studied.
We have shown for the first time IDE staining in
rodent and human tissue, using the proper negative
control, IDE null mouse tissue. Our staining indicates
that IDE is expressed in both beta- and alpha-cells, with
higher expression in alpha-cells. Db/db and HFD mice
islets showed increased IDE protein level. Interestingly,
human islets from DM2 patients treated with OHAs
showed decreased IDE protein level in beta-cells.
Meanwhile, islets from insulin-treated DM2 patients
showed augmented IDE protein level compared to
OHAs patients, pointing to an upregulation of IDE
protein level stimulated by insulin. These data correlate
nicely with insulin-stimulated upregulation of IDE in
cultured INS1E cells, as well as in rat and human islets.In conclusion, our study shows that IDE is expressed
in pancreatic beta- and alpha-cells of both rodents and
humans, having higher expression in alpha-cells.
Furthermore, insulin stimulates IDE protein level in
pancreatic beta-cells. These results may have
implications in how DM2 patient’s treatment affects
their beta-cell function.
Insulin-degrading enzyme Type 2 diabetes, Insulin treatment, OHAs Beta-cells Alpha-cells Rodent islets Human islets