title: Beta-Cell Injury in Ncb5or-null Mice is Exacerbated by Consumption of a High-Fat Diet.
abstract: NADH-cytochrome b5 oxidoreductase (Ncb5or) in endoplasmic reticulum (ER) is involved in fatty acid metabolism, and Ncb5or(-/-) mice fed standard chow (SC) are insulin-sensitive but weigh less than wild type (WT) littermates. Ncb5or(-/-) mice develop hyperglycemia at about age 7 weeks due to β-cell dysfunction and loss associated with saturated fatty acid accumulation and manifestations of ER and oxidative stress. Here we report that when Ncb5or(-/-) mice born to heterozygous mothers fed a high fat (HF) diet continue to ingest HF, they weigh as much as SC-fed WT at age 5 weeks. By age 7 weeks, diabetes mellitus develops in all HF-fed vs. 68% of SC-fed Ncb5or(-/-) mice. Islet β-cell content in age 5-week Ncb5or(-/-) mice fed HF for 7 days is lower (53%) than for those fed SC (63%), and both are lower than for WT (75%, SC, vs. 69%, HF). Islet transcript levels for markers of mitochondrial biogenesis (PGC-1α) and ER stress (ATF6α) are higher in Ncb5or(-/-) than WT mice but not significantly affected by diet. Consuming a HF diet exacerbates Ncb5or(-/-) β-cell accumulation of intracellular saturated fatty acids and increases the frequency of ER distention from 11% (SC) to 47% (HF), thus accelerates β-cell injury in Ncb5or(-/-) mice.
authors.affiliation: Department of Endocrinology, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 510275.
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Bin
authors.initials: B
authors.lastname: Deng
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Frontera
authors.forename: Karen L
authors.initials: KL
authors.lastname: Kover
authors.forename: Daniel
authors.initials: D
authors.lastname: Aires
authors.forename: Helin
authors.initials: H
authors.lastname: Ding
authors.forename: Susan E
authors.initials: SE
authors.lastname: Carlson
authors.forename: John
authors.initials: J
authors.lastname: Turk
authors.forename: Wenfang
authors.initials: W
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhu