Chronic high-glucose treatment causes ER stress in islets and insulinoma cells, resulting in a reduction in insulin gene expression.

<p>(A) Islets pooled from 6 mice were treated with 5 mM, 11 mM, or 16.7 mM glucose for 24 or 72 hr. Expression levels of Ero1α, Chop, spliced Xbp-1, and total Xbp-1 were measured by real- time PCR (n = 2). (B) Islets pooled from 6 mice were treated with 5 mM, 11 mM, or 16.7 mM glucose for 24 or 72 hr. Expression levels of Insulin 1 and Insulin 2 were measured by real time PCR (n = 2). (C) INS-1 832/13 cells were pretreated for 12 hr with 5 mM glucose, then treated with 5 mM, 11 mM, or 16.7 mM glucose for 72 hr. Expression levels of Insulin 1, Insulin 2, and spliced Xbp-1 were measured by real time PCR (n = 3; values are mean±SEM). (D) INS-1 832/13 cells were pretreated for 12 hr with 5 mM glucose, then treated with 5 mM, 11 mM, or 16.7 mM glucose for 72 hr. Total IRE1α, phosphorylated IRE1α, and actin were measured by immunoblot.