The combination of loss of glyoxalase1 and obesity results in hyperglycemia

• Verfasst von: Lodd, Elisabeth [VerfasserIn]
• Verfasst von: Wiggenhauser, Lucas [VerfasserIn]
• Verfasst von: Morgenstern, Jakob [VerfasserIn]
• Verfasst von: Fleming, Thomas [VerfasserIn]
• Verfasst von: Poschet, Gernot [VerfasserIn]
• Verfasst von: Büttner, Michael [VerfasserIn]
• Verfasst von: Tabler, Christoph Tobias [VerfasserIn]
• Verfasst von: Wohlfart, David Philipp [VerfasserIn]
• Verfasst von: Nawroth, Peter Paul [VerfasserIn]
• Verfasst von: Kroll, Jens [VerfasserIn]
• Titel: The combination of loss of glyoxalase1 and obesity results in hyperglycemia
• Verf.angabe: Elisabeth Lodd, Lucas M. Wiggenhauser, Jakob Morgenstern, Thomas H. Fleming, Gernot Poschet, Michael Büttner, Christoph T. Tabler, David P. Wohlfart, Peter P. Nawroth, Jens Kroll
• E-Jahr: 2019
• Jahr: June 20, 2019
• Fussnoten: Published June 20, 2019 ; Gesehen am 06.11.2019
• Titel Quelle: Enthalten in: JCI insight
• Ort Quelle: Ann Arbor, Michigan : JCI Insight, 2016
• Jahr Quelle: 2019
• Band/Heft Quelle: 4(2019,12) Artikel-Nummer e126154, 17 Seiten
• ISSN Quelle: 2379-3708
• DOI: doi:10.1172/jci.insight.126154
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1681173158

Abstract

The increased formation of methylglyoxal (MG) under hyperglycemia is associated with the development of microvascular complications in patients with diabetes mellitus; however, the effects of elevated MG levels in vivo are poorly understood. In zebrafish, a transient knockdown of glyoxalase 1, the main MG detoxifying system, led to the elevation of endogenous MG levels and blood vessel alterations. To evaluate effects of a permanent knockout of glyoxalase 1 in vivo, glo1–/– zebrafish mutants were generated using CRISPR/Cas9. In addition, a diet-induced–obesity zebrafish model was used to analyze glo1–/– zebrafish under high nutrient intake. Glo1–/– zebrafish survived until adulthood without growth deficit and showed increased tissue MG concentrations. Impaired glucose tolerance developed in adult glo1–/– zebrafish and was indicated by increased postprandial blood glucose levels and postprandial S6 kinase activation. Challenged by an overfeeding period, fasting blood glucose levels in glo1–/– zebrafish were increased which translated into retinal blood vessel alterations. Thus, the data have identified a defective MG detoxification as a metabolic prerequisite and glyoxalase 1 alterations as a genetic susceptibility to the development of type 2 diabetes mellitus under high nutrition intake.