Regulation of glucose metabolism by MuRF1 and treatment of myopathy in diabetic mice with small molecules targeting MuRF1
The muscle-specific ubiquitin ligase MuRF1 regulates muscle catabolism during chronic wasting states, although its roles in general metabolism are less-studied. Here, we metabolically profiled MuRF1-deficient knockout mice. We also included knockout mice for MuRF2 as its closely related gene homolog...
Gespeichert in:
| Hauptverfasser: | , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
23 February 2021
|
| In: |
International journal of molecular sciences
Year: 2021, Jahrgang: 22, Heft: 4, Pages: 1-14 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22042225 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/ijms22042225 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/1422-0067/22/4/2225 
|
| Verfasserangaben: | Siegfried Labeit, Stephanie Hirner, Julijus Bogomolovas, André Cruz, Moldir Myrzabekova, Anselmo Moriscot, Thomas Scott Bowen and Volker Adams |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1757004408 | ||
| 003 | DE-627 | ||
| 005 | 20230426114222.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 210503s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ijms22042225 |2 doi | |
| 035 | |a (DE-627)1757004408 | ||
| 035 | |a (DE-599)KXP1757004408 | ||
| 035 | |a (OCoLC)1341407795 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Labeit, Siegfried |d 1960- |e VerfasserIn |0 (DE-588)1033566837 |0 (DE-627)741562375 |0 (DE-576)381187314 |4 aut | |
| 245 | 1 | 0 | |a Regulation of glucose metabolism by MuRF1 and treatment of myopathy in diabetic mice with small molecules targeting MuRF1 |c Siegfried Labeit, Stephanie Hirner, Julijus Bogomolovas, André Cruz, Moldir Myrzabekova, Anselmo Moriscot, Thomas Scott Bowen and Volker Adams |
| 264 | 1 | |c 23 February 2021 | |
| 300 | |a 14 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 03.05.2021 | ||
| 520 | |a The muscle-specific ubiquitin ligase MuRF1 regulates muscle catabolism during chronic wasting states, although its roles in general metabolism are less-studied. Here, we metabolically profiled MuRF1-deficient knockout mice. We also included knockout mice for MuRF2 as its closely related gene homolog. MuRF1 and MuRF2-KO (knockout) mice have elevated serum glucose, elevated triglycerides, and reduced glucose tolerance. In addition, MuRF2-KO mice have a reduced tolerance to a fat-rich diet. Western blot and enzymatic studies on MuRF1-KO skeletal muscle showed perturbed FoxO-Akt signaling, elevated Akt-Ser-473 activation, and downregulated oxidative mitochondrial metabolism, indicating potential mechanisms for MuRF1,2-dependent glucose and fat metabolism regulation. Consistent with this, the adenoviral re-expression of MuRF1 in KO mice normalized Akt-Ser-473, serum glucose, and triglycerides. Finally, we tested the MuRF1/2 inhibitors MyoMed-205 and MyoMed-946 in a mouse model for type 2 diabetes mellitus (T2DM). After 28 days of treatment, T2DM mice developed progressive muscle weakness detected by wire hang tests, but this was attenuated by the MyoMed-205 treatment. While MyoMed-205 and MyoMed-946 had no significant effects on serum glucose, they did normalize the lymphocyte-granulocyte counts in diabetic sera as indicators of the immune response. Thus, small molecules directed to MuRF1 may be useful in attenuating skeletal muscle strength loss in T2DM conditions. | ||
| 650 | 4 | |a chemical biology | |
| 650 | 4 | |a diabetes mellitus | |
| 650 | 4 | |a glucose and muscle metabolism | |
| 650 | 4 | |a MuRF1 | |
| 650 | 4 | |a MuRF2 | |
| 700 | 1 | |a Hirner, Stephanie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bogomolovas, Julijus |e VerfasserIn |4 aut | |
| 700 | 1 | |a Cruz, André |e VerfasserIn |4 aut | |
| 700 | 1 | |a Myrzabekova, Moldir |e VerfasserIn |4 aut | |
| 700 | 1 | |a Moriscot, Anselmo |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bowen, Thomas Scott |e VerfasserIn |4 aut | |
| 700 | 1 | |a Adams, Volker |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d Basel : Molecular Diversity Preservation International, 2000 |g 22(2021), 4, Artikel-ID 2225, Seite 1-14 |h Online-Ressource |w (DE-627)316340715 |w (DE-600)2019364-6 |w (DE-576)281194653 |x 1422-0067 |7 nnas |a Regulation of glucose metabolism by MuRF1 and treatment of myopathy in diabetic mice with small molecules targeting MuRF1 |
| 773 | 1 | 8 | |g volume:22 |g year:2021 |g number:4 |g elocationid:2225 |g pages:1-14 |g extent:14 |a Regulation of glucose metabolism by MuRF1 and treatment of myopathy in diabetic mice with small molecules targeting MuRF1 |
| 856 | 4 | 0 | |u https://doi.org/10.3390/ijms22042225 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.mdpi.com/1422-0067/22/4/2225 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20210503 | ||
| 993 | |a Article | ||
| 994 | |a 2021 | ||
| 998 | |g 1033566837 |a Labeit, Siegfried |m 1033566837:Labeit, Siegfried |d 60000 |d 61600 |e 60000PL1033566837 |e 61600PL1033566837 |k 0/60000/ |k 1/60000/61600/ |p 1 |x j | ||
| 999 | |a KXP-PPN1757004408 |e 392175660X | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"name":{"displayForm":["Siegfried Labeit, Stephanie Hirner, Julijus Bogomolovas, André Cruz, Moldir Myrzabekova, Anselmo Moriscot, Thomas Scott Bowen and Volker Adams"]},"person":[{"family":"Labeit","display":"Labeit, Siegfried","role":"aut","given":"Siegfried"},{"family":"Hirner","role":"aut","given":"Stephanie","display":"Hirner, Stephanie"},{"role":"aut","given":"Julijus","display":"Bogomolovas, Julijus","family":"Bogomolovas"},{"family":"Cruz","given":"André","role":"aut","display":"Cruz, André"},{"family":"Myrzabekova","display":"Myrzabekova, Moldir","given":"Moldir","role":"aut"},{"family":"Moriscot","given":"Anselmo","role":"aut","display":"Moriscot, Anselmo"},{"display":"Bowen, Thomas Scott","role":"aut","given":"Thomas Scott","family":"Bowen"},{"display":"Adams, Volker","given":"Volker","role":"aut","family":"Adams"}],"recId":"1757004408","origin":[{"dateIssuedDisp":"23 February 2021","dateIssuedKey":"2021"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"physDesc":[{"extent":"14 S."}],"id":{"eki":["1757004408"],"doi":["10.3390/ijms22042225"]},"relHost":[{"part":{"issue":"4","pages":"1-14","extent":"14","volume":"22","text":"22(2021), 4, Artikel-ID 2225, Seite 1-14","year":"2021"},"language":["eng"],"title":[{"title_sort":"International journal of molecular sciences","title":"International journal of molecular sciences"}],"pubHistory":["1.2000 -"],"recId":"316340715","origin":[{"publisherPlace":"Basel","dateIssuedKey":"2000","dateIssuedDisp":"2000-","publisher":"Molecular Diversity Preservation International"}],"type":{"media":"Online-Ressource","bibl":"periodical"},"titleAlt":[{"title":"IJMS"}],"note":["Gesehen am 17.09.20"],"disp":"Regulation of glucose metabolism by MuRF1 and treatment of myopathy in diabetic mice with small molecules targeting MuRF1International journal of molecular sciences","physDesc":[{"extent":"Online-Ressource"}],"id":{"issn":["1422-0067","1661-6596"],"zdb":["2019364-6"],"eki":["316340715"]}}],"note":["Gesehen am 03.05.2021"],"title":[{"title":"Regulation of glucose metabolism by MuRF1 and treatment of myopathy in diabetic mice with small molecules targeting MuRF1","title_sort":"Regulation of glucose metabolism by MuRF1 and treatment of myopathy in diabetic mice with small molecules targeting MuRF1"}],"language":["eng"]} | ||
| SRT | |a LABEITSIEGREGULATION2320 | ||