Estrogens Promote Misfolded Proinsulin Degradation to Protect Insulin Production and Delay Diabetes.
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ABSTRACT:
SUBMITTER: Xu B
PROVIDER: S-EPMC6092934 | biostudies-literature | 2018 Jul
REPOSITORIES: biostudies-literature
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Estrogens Promote Misfolded Proinsulin Degradation to Protect Insulin Production and Delay Diabetes.
Xu Beibei B Allard Camille C Alvarez-Mercado Ana I AI Fuselier Taylor T Kim Jun Ho JH Coons Laurel A LA Hewitt Sylvia C SC Urano Fumihiko F Korach Kenneth S KS Levin Ellis R ER Arvan Peter P Floyd Z Elizabeth ZE Mauvais-Jarvis Franck F
Cell reports 20180701 1
Conjugated estrogens (CE) delay the onset of type 2 diabetes (T2D) in postmenopausal women, but the mechanism is unclear. In T2D, the endoplasmic reticulum (ER) fails to promote proinsulin folding and, in failing to do so, promotes ER stress and β cell dysfunction. We show that CE prevent insulin-deficient diabetes in male and in female Akita mice using a model of misfolded proinsulin. CE stabilize the ER-associated protein degradation (ERAD) system and promote misfolded proinsulin proteasomal d ...[more]
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