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- Mattis, Katia K, et al.
(författare)
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Loss of RREB1 in pancreatic beta cells reduces cellular insulin content and affects endocrine cell gene expression
- 2023
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Ingår i: Diabetologia. - : Springer Nature. - 0012-186X .- 1432-0428. ; 66:4, s. 674-694
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Genome-wide studies have uncovered multiple independent signals at the RREB1 locus associated with altered type 2 diabetes risk and related glycaemic traits. However, little is known about the function of the zinc finger transcription factor Ras-responsive element binding protein 1 (RREB1) in glucose homeostasis or how changes in its expression and/or function influence diabetes risk.METHODS: A zebrafish model lacking rreb1a and rreb1b was used to study the effect of RREB1 loss in vivo. Using transcriptomic and cellular phenotyping of a human beta cell model (EndoC-βH1) and human induced pluripotent stem cell (hiPSC)-derived beta-like cells, we investigated how loss of RREB1 expression and activity affects pancreatic endocrine cell development and function. Ex vivo measurements of human islet function were performed in donor islets from carriers of RREB1 type 2 diabetes risk alleles.RESULTS: CRISPR/Cas9-mediated loss of rreb1a and rreb1b function in zebrafish supports an in vivo role for the transcription factor in beta cell mass, beta cell insulin expression and glucose levels. Loss of RREB1 also reduced insulin gene expression and cellular insulin content in EndoC-βH1 cells and impaired insulin secretion under prolonged stimulation. Transcriptomic analysis of RREB1 knockdown and knockout EndoC-βH1 cells supports RREB1 as a novel regulator of genes involved in insulin secretion. In vitro differentiation of RREB1KO/KO hiPSCs revealed dysregulation of pro-endocrine cell genes, including RFX family members, suggesting that RREB1 also regulates genes involved in endocrine cell development. Human donor islets from carriers of type 2 diabetes risk alleles in RREB1 have altered glucose-stimulated insulin secretion ex vivo, consistent with a role for RREB1 in regulating islet cell function.CONCLUSIONS/INTERPRETATION: Together, our results indicate that RREB1 regulates beta cell function by transcriptionally regulating the expression of genes involved in beta cell development and function.
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- Gupta, Rahul, et al.
(författare)
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Engineering of spin mixing conductance at Ru/FeCo/Ru interfaces : Effect of Re doping
- 2020
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - : AMER PHYSICAL SOC. - 1098-0121 .- 1550-235X. ; 101:2
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Tidskriftsartikel (refereegranskat)abstract
- We have deposited polycrystalline Re-doped (Fe65Co35)(100-x)Rex (0 ≤ x ≤ 12.6 at. %) thin films grown under identical conditions and sandwiched between thin layers of Ru in order to study the phenomenon of spin pumping as a function of Re concentration. In-plane and out-of-plane ferromagnetic resonance spectroscopy results show an enhancement of the Gilbert damping with an increase in Re doping. We find 98% enhancement in the real part of effective spin mixing conductance [Re(g↑↓eff)] with Re doping. Conversely, the Re(g↑↓eff) does not change with Re doping in Fe65Co35 thin films which are seeded and capped with Cu layers. The enhancement in Re(g↑↓eff) of Re-doped Fe65Co35 thin films sandwiched between thin layers of Ru is linked to the Re doping-induced change of the interface electronic structure in the nonmagnetic Ru layer. The saturation magnetization decreases 35% with increasing Re doping up to 12.6 at. %. This study opens a direction of tuning the spin mixing conductance in magnetic heterostructures by doping of the ferromagnetic layer, which is essential for the realization of energyefficient operation of spintronic devices.
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