| 1. |
- He, Shijun, et al.
(author)
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GLP-1 Receptor Activation Abrogates β-Cell Dysfunction by PKA Cα-Mediated Degradation of Thioredoxin Interacting Protein
- 2019
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In: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 10
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Journal article (peer-reviewed)abstract
- Glucagon-like peptide 1 receptor (GLP-1R) agonist (Exendin-4) is a well-known agent used to improve β-cell dysfunctions via protein kinase A (PKA), but the detailed downstream molecular mechanisms are still elusive. We have now found that PKA Cα mediated- TXNIP phosphorylation and degradation played a vital role in the β-cell protective role of exendin-4. After PKA activator (Exendin-4 or FSK) treatment, PKA Cα could directly interact with TXNIP by bimolecular fluorescence complementation and Co-IP assays in INS-1 cells. And PKA Cα overexpression decreased TXNIP level, whereas TXNIP level was largely increased in PKA Cα-KO β-cells by CRISPR-Cas9. Interestingly, TXNIP overexpression or PKA Cα-KO has impaired β-cell functions, including loss of insulin secretion and activation of inflammation. PKA Cα directly phosphorylated TXNIP at Ser307 and Ser308 positions, leading to its degradation via activation of cellular proteasome pathway. Consistent with this observation, TXNIP (S307/308A) mutant resisted the degradation effects of PKA Cα. However, exendin-4 neither affected TXNIP level in TXNIP (S307/308A) mutant overexpressed β-cells nor in PKA Cα-KO β-cells. Moreover, exendin-4 treatment reduced the inflammation gene expression in TXNIP overexpressed β-cells, but exendin-4 treatment has no effect on the inflammation gene expression in TXNIP (S307/308A) overexpressed β-cells. In conclusion, our study reveals the integral role of PKA Cα/TXNIP signaling in pancreatic β-cells and suggests that PKA Cα-mediated TXNIP degradation is vital in β-cell protective effects of exendin-4.
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| 2. |
- Tian, Kai, et al.
(author)
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Comprehensive Characterization of the 4H-SiC Planar and Trench Gate MOSFETs From Cryogenic to High Temperature
- 2019
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In: IEEE Transactions on Electron Devices. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 0018-9383 .- 1557-9646. ; 66:10, s. 4279-4286
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Journal article (peer-reviewed)abstract
- In this article, the static, dynamic, and short-circuit properties of 1.2-kV commercial 4H-SiC planar and trench gate metal-oxide-semiconductor field-effect transistors (MOSFETs) are compared and analyzed in a wide temperature range from 90 to 493 K. The temperature-dependent specific ON-resistance (Rsp-ON) and threshold voltage (V-th) are analyzed in relation to the density of the interface state. The turn-on rise and turn-off fall times (T-r and T-f) and the corresponding energy loss (E-r and E-f) are extracted from a double-pulse test from cryogenic to high temperature and analyzed. The short-circuit capability of the two structures is studied at low temperature for the first time. The comprehensive comparison and analysis of the planar and trench gate MOSFET versus temperature in this work show the importance to study applications with SiC MOSFETs in a wide temperature range, especially for the cryogenic temperatures.
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