Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes
Objectives - The deficit of Glyoxalase I (Glo1) and the subsequent increase in methylglyoxal (MG) has been reported to be one the five mechanisms by which hyperglycemia causes diabetic late complications. Aldo-keto reductases (AKR) have been shown to metabolize MG; however, the relative contribution...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
19 September 2018
|
| In: |
Molecular metabolism
Year: 2018, Volume: 18, Pages: 143-152 |
| ISSN: | 2212-8778 |
| DOI: | 10.1016/j.molmet.2018.09.005 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.molmet.2018.09.005 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S2212877818302047 
|
| Author Notes: | Dagmar Schumacher, Jakob Morgenstern, Yoko Oguchi, Nadine Volk, Stefan Kopf, Jan Benedikt Groener, Peter Paul Nawroth, Thomas Fleming, Marc Freichel |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1672329620 | ||
| 003 | DE-627 | ||
| 005 | 20240323101250.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 190828s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.molmet.2018.09.005 |2 doi | |
| 035 | |a (DE-627)1672329620 | ||
| 035 | |a (DE-599)KXP1672329620 | ||
| 035 | |a (OCoLC)1341238561 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Schumacher, Dagmar |e VerfasserIn |0 (DE-588)1185585869 |0 (DE-627)1664964770 |4 aut | |
| 245 | 1 | 0 | |a Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes |c Dagmar Schumacher, Jakob Morgenstern, Yoko Oguchi, Nadine Volk, Stefan Kopf, Jan Benedikt Groener, Peter Paul Nawroth, Thomas Fleming, Marc Freichel |
| 264 | 1 | |c 19 September 2018 | |
| 300 | |a 10 | ||
| 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 28.08.2019 | ||
| 520 | |a Objectives - The deficit of Glyoxalase I (Glo1) and the subsequent increase in methylglyoxal (MG) has been reported to be one the five mechanisms by which hyperglycemia causes diabetic late complications. Aldo-keto reductases (AKR) have been shown to metabolize MG; however, the relative contribution of this superfamily to the detoxification of MG in vivo, particularly within the diabetic state, remains unknown. - Methods - CRISPR/Cas9-mediated genome editing was used to generate a Glo1 knock-out (Glo1−/−) mouse line. Streptozotocin was then applied to investigate metabolic changes under hyperglycemic conditions. - Results - Glo1−/− mice were viable and showed no elevated MG or MG-H1 levels under hyperglycemic conditions. It was subsequently found that the enzymatic efficiency of various oxidoreductases in the liver and kidney towards MG were increased in the Glo1−/− mice. The functional relevance of this was supported by the altered distribution of alternative detoxification products. Furthermore, it was shown that MG-dependent AKR activity is a potentially clinical relevant pathway in human patients suffering from diabetes. - Conclusions - These data suggest that in the absence of GLO1, AKR can effectively compensate to prevent the accumulation of MG. The combination of metabolic, enzymatic, and genetic factors, therefore, may provide a better means of identifying patients who are at risk for the development of late complications caused by elevated levels of MG. | ||
| 650 | 4 | |a Advanced glycation end products | |
| 650 | 4 | |a Aldo-keto reductases | |
| 650 | 4 | |a Diabetic complications | |
| 650 | 4 | |a Glyoxalase 1 | |
| 650 | 4 | |a Methylglyoxal | |
| 650 | 4 | |a Reactive metabolites | |
| 700 | 1 | |a Morgenstern, Jakob |d 1985- |e VerfasserIn |0 (DE-588)1129805832 |0 (DE-627)884397599 |0 (DE-576)486560864 |4 aut | |
| 700 | 1 | |a Oguchi, Yoko |e VerfasserIn |0 (DE-588)1193597021 |0 (DE-627)1672326990 |4 aut | |
| 700 | 1 | |a Volk, Nadine |d 1986- |e VerfasserIn |0 (DE-588)1160966214 |0 (DE-627)1024357368 |0 (DE-576)506288595 |4 aut | |
| 700 | 1 | |a Kopf, Stefan |d 1978- |e VerfasserIn |0 (DE-588)1013047516 |0 (DE-627)663343453 |0 (DE-576)346399025 |4 aut | |
| 700 | 1 | |a Gröner, Jan |e VerfasserIn |0 (DE-588)1017332444 |0 (DE-627)676373771 |0 (DE-576)353490172 |4 aut | |
| 700 | 1 | |a Nawroth, Peter Paul |d 1954- |e VerfasserIn |0 (DE-588)1020504897 |0 (DE-627)69123941X |0 (DE-576)360517692 |4 aut | |
| 700 | 1 | |a Fleming, Thomas |d 1982- |e VerfasserIn |0 (DE-588)1034445294 |0 (DE-627)745607365 |0 (DE-576)382066804 |4 aut | |
| 700 | 1 | |a Freichel, Marc |d 1968- |e VerfasserIn |0 (DE-588)17286819X |0 (DE-627)697797147 |0 (DE-576)133723615 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Molecular metabolism |d Oxford [u.a.] : Elsevier, 2012 |g 18(2018), Seite 143-152 |h Online-Ressource |w (DE-627)739898752 |w (DE-600)2708735-9 |w (DE-576)380470314 |x 2212-8778 |7 nnas |a Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes |
| 773 | 1 | 8 | |g volume:18 |g year:2018 |g pages:143-152 |g extent:10 |a Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.molmet.2018.09.005 |x Verlag |x Resolving-System |3 Volltext |
| 856 | 4 | 0 | |u http://www.sciencedirect.com/science/article/pii/S2212877818302047 |x Verlag |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20190828 | ||
| 993 | |a Article | ||
| 994 | |a 2018 | ||
| 998 | |g 17286819X |a Freichel, Marc |m 17286819X:Freichel, Marc |d 50000 |d 54600 |e 50000PF17286819X |e 54600PF17286819X |k 0/50000/ |k 1/50000/54600/ |p 9 |y j | ||
| 998 | |g 1034445294 |a Fleming, Thomas |m 1034445294:Fleming, Thomas |d 910000 |d 910100 |e 910000PF1034445294 |e 910100PF1034445294 |k 0/910000/ |k 1/910000/910100/ |p 8 | ||
| 998 | |g 1020504897 |a Nawroth, Peter Paul |m 1020504897:Nawroth, Peter Paul |d 910000 |d 910100 |e 910000PN1020504897 |e 910100PN1020504897 |k 0/910000/ |k 1/910000/910100/ |p 7 | ||
| 998 | |g 1017332444 |a Gröner, Jan |m 1017332444:Gröner, Jan |d 910000 |d 910100 |e 910000PG1017332444 |e 910100PG1017332444 |k 0/910000/ |k 1/910000/910100/ |p 6 | ||
| 998 | |g 1013047516 |a Kopf, Stefan |m 1013047516:Kopf, Stefan |d 910000 |d 910100 |e 910000PK1013047516 |e 910100PK1013047516 |k 0/910000/ |k 1/910000/910100/ |p 5 | ||
| 998 | |g 1160966214 |a Volk, Nadine |m 1160966214:Volk, Nadine |d 910000 |d 912000 |e 910000PV1160966214 |e 912000PV1160966214 |k 0/910000/ |k 1/910000/912000/ |p 4 | ||
| 998 | |g 1193597021 |a Oguchi, Yoko |m 1193597021:Oguchi, Yoko |d 50000 |e 50000PO1193597021 |k 0/50000/ |p 3 | ||
| 998 | |g 1129805832 |a Morgenstern, Jakob |m 1129805832:Morgenstern, Jakob |d 910000 |d 910100 |e 910000PM1129805832 |e 910100PM1129805832 |k 0/910000/ |k 1/910000/910100/ |p 2 | ||
| 998 | |g 1185585869 |a Schumacher, Dagmar |m 1185585869:Schumacher, Dagmar |d 50000 |d 54600 |e 50000PS1185585869 |e 54600PS1185585869 |k 0/50000/ |k 1/50000/54600/ |p 1 |x j | ||
| 999 | |a KXP-PPN1672329620 |e 3509349954 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"note":["Gesehen am 28.08.2019"],"person":[{"role":"aut","display":"Schumacher, Dagmar","given":"Dagmar","family":"Schumacher"},{"role":"aut","display":"Morgenstern, Jakob","family":"Morgenstern","given":"Jakob"},{"display":"Oguchi, Yoko","family":"Oguchi","given":"Yoko","role":"aut"},{"given":"Nadine","family":"Volk","display":"Volk, Nadine","role":"aut"},{"display":"Kopf, Stefan","family":"Kopf","given":"Stefan","role":"aut"},{"family":"Gröner","given":"Jan","display":"Gröner, Jan","role":"aut"},{"given":"Peter Paul","family":"Nawroth","display":"Nawroth, Peter Paul","role":"aut"},{"family":"Fleming","given":"Thomas","display":"Fleming, Thomas","role":"aut"},{"display":"Freichel, Marc","family":"Freichel","given":"Marc","role":"aut"}],"title":[{"title":"Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes","title_sort":"Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes"}],"origin":[{"dateIssuedDisp":"19 September 2018","dateIssuedKey":"2018"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"physDesc":[{"extent":"10 S."}],"language":["eng"],"recId":"1672329620","id":{"doi":["10.1016/j.molmet.2018.09.005"],"eki":["1672329620"]},"relHost":[{"note":["Gesehen am 25.06.20"],"title":[{"title":"Molecular metabolism","subtitle":"official journal of the German Center for Diabetes Research (DZD)","title_sort":"Molecular metabolism"}],"pubHistory":["1.2012 -"],"origin":[{"dateIssuedKey":"2012","dateIssuedDisp":"2012-","publisher":"Elsevier","publisherPlace":"Oxford [u.a.]"}],"type":{"bibl":"periodical","media":"Online-Ressource"},"disp":"Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetesMolecular metabolism","physDesc":[{"extent":"Online-Ressource"}],"part":{"extent":"10","volume":"18","pages":"143-152","text":"18(2018), Seite 143-152","year":"2018"},"language":["eng"],"recId":"739898752","id":{"issn":["2212-8778"],"zdb":["2708735-9"],"eki":["739898752"]}}],"name":{"displayForm":["Dagmar Schumacher, Jakob Morgenstern, Yoko Oguchi, Nadine Volk, Stefan Kopf, Jan Benedikt Groener, Peter Paul Nawroth, Thomas Fleming, Marc Freichel"]}} | ||
| SRT | |a SCHUMACHERCOMPENSATO1920 | ||