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PXD035076-1

PXD035076 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePhenylalanine Impairs Insulin Signaling and Inhibits Glucose Uptake Through Modification of IRβ
DescriptionWhether amino acids act on cellular insulin signaling remains unclear, given that increased circulating amino acid levels are associated with the onset of type 2 diabetes (T2D). Here, we report that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake. Mice fed phenylalanine-rich chow or phenylalanine-producing aspartame or overexpressing human phenylalanyl-tRNA synthetase (hFARS) developed insulin resistance and T2D symptoms. Mechanistically, FARS phenylalanylated lysine 1057/1079 of IRβ (F-K1057/1079), inactivating IRβ and preventing insulin from promoting glucose uptake by cells. SIRT1 reversed F-K1057/1079 and counteracted the insulin-inactivating effects of hFARS and phenylalanine. F-K1057/1079 and SIRT1 levels in white blood cells from T2D patients wereare positively and negatively correlated with T2D onset, respectively. Blocking F-K1057/1079 with phenylalaninol sensitizeds insulin signaling and relieveds T2D symptoms in hFARS-transgenic and db/db mice. These findings shed light on the activation of insulin signaling and T2D progression through inhibition of phenylalanylation.
HostingRepositoryPRIDE
AnnounceDate2022-07-22
AnnouncementXMLSubmission_2022-07-22_04:17:22.366.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterQian Zhou
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmodified L-phenylalanine residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-07-04 14:52:56ID requested
12022-07-22 04:17:22announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Insulin receptor,phenylalanylation,Type 2 diabetes
Contact List
Shi-Min Zhao
contact affiliationObstetrics & Gynecology Institute, Institute of Metabolism and Integrative Biology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
contact emailzhaosm@fudan.edu.cn
lab head
Qian Zhou
contact affiliation86-13162869989
contact email953975702@qq.com
dataset submitter
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Dataset FTP location
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