Dietary restriction induces a sexually dimorphic type I interferon response in mice with gene-environment interactions

Harney, Dylan; Cielesh, Michelle; Roberts, George E.; Vila, Isabelle K.; Viengkhou, Barney; Höfer, Markus; Laguette, Nadine; Larance, Mark

doi:10.1016/j.celrep.2023.112559

Cited by 4 publications

(2 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Protein samples for bottom-up proteomics analysis were prepared as describe previously[21]. Briefly, proteins were extracted in a buffer containing 4% sodium deoxycholate (SDC), 40 mM chloroacetamide, 10 mM TCEP and 0.1 M Tris-HCl (pH 8.0) in water.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

VPS41 deletion triggers progressive loss of insulin stores and downregulation of beta-cell identity

Yau,

An,

Germanos

et al. 2024

Preprint

View full text Add to dashboard Cite

Vacuolar protein sorting-associated protein 41 (VPS41) has previously been established as a requirement for normal insulin secretory function in pancreatic beta-cells, with genetic deletion of VPS41 in insulinoma cells (VPS41KO) resulting in defects in insulin granule composition and secretory behaviour. In mice, VPS41 deletion in pancreatic beta-cells presented as severe hyperglycaemia due to an insulin insufficiency. Presently, we show that chronic VPS41 deletion modelled in VPS41KO insulinoma cells and aged VPS41 beta-cell knockout mice results in beta-cell dedifferentiation associated with downregulation of beta-cell identity genes and insulin granule pathway proteins. In mice, a sexually dimorphic response to beta-cell specific VPS41 deletion is observed, with young female mice exhibiting preserved insulin content, less upregulation of degradation pathway-associated proteins, and reduced ER stress, compared to young male mice. In an acute model of VPS41 depletion in vitro, VPS41-dependent loss of insulin is associated with cytosolic redistribution of mammalian target of rapamycin (mTOR), increased nuclear localisation of transcription factor E3, and impaired autophagy in VPS41KD cells. Inhibition of lysosomal degradation with chloroquine or a cysteine protease inhibitor rescues the rapidly depleted insulin content. This phenotype reflects a HOPS-dependent mechanism for insulin content regulation, with VPS41 functioning as a critical component.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Samples were mixed with ethyl acetate (50% final concentration, v/v), vortexed until SDC precipitates dissolved. SDB-RPS StageTips were prepared, sample purification performed as described previously[21]. Peptides were reconstituted with 5 % formic acid in MS-grade H2O, sealed and stored at 4 °C until LC-MS/MS acquisition.…”

Section: Methodsmentioning

confidence: 99%