Effects of the Reactive Metabolite Methylglyoxal on Cellular Signalling, Insulin Action and Metabolism – What We Know in Mammals and What We Can Learn From Yeast

Johanna Zemva; Daniel Pfaff; Jan B. Groener; Thomas Fleming; Stephan Herzig; Aurelio Teleman; Peter P. Nawroth; Jens Tyedmers

doi:10.1055/s-0043-122382

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2019; 127(04): 203-214
DOI: 10.1055/s-0043-122382

Review

Effects of the Reactive Metabolite Methylglyoxal on Cellular Signalling, Insulin Action and Metabolism – What We Know in Mammals and What We Can Learn From Yeast

Johanna Zemva

¹Department of Medicine I and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany

,

Daniel Pfaff

¹Department of Medicine I and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany

²German Cancer Research Center (DKFZ), Heidelberg, Germany

,

Jan B. Groener

¹Department of Medicine I and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany

⁴German Center for Diabetes Research (DZD), München-Neuherberg, Germany

,

Thomas Fleming

¹Department of Medicine I and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany

⁴German Center for Diabetes Research (DZD), München-Neuherberg, Germany

,

Stephan Herzig

³Joint Heidelberg-IDC Translational Diabetes Program, Dept. Inner Medicine I, Heidelberg University Hospital, Germany

⁵Institute for Diabetes and Cancer IDC, Helmholtz Center Munich, Germany

,

Aurelio Teleman

²German Cancer Research Center (DKFZ), Heidelberg, Germany

,

Peter P. Nawroth

¹Department of Medicine I and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany

³Joint Heidelberg-IDC Translational Diabetes Program, Dept. Inner Medicine I, Heidelberg University Hospital, Germany

⁴German Center for Diabetes Research (DZD), München-Neuherberg, Germany

,

Jens Tyedmers

¹Department of Medicine I and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany

› Author Affiliations

Abstract

Levels of reactive metabolites such as reactive carbonyl and oxygen species are increased in patients with diabetes mellitus. The most important reactive dicarbonyl species, methylglyoxal (MG), formed as by-product during glucose metabolism, is more and more recognized as a trigger for the development and progression of diabetic complications. Although it is clear that MG provokes toxic effects, it is currently not well understood what cellular changes MG induces on a molecular level that may lead to pathophysiological conditions found in long-term diabetic complications. Here we review the current knowledge about the molecular effects that MG can induce in a cell. Within the mammalian system, we will focus mostly on the metabolic effects MG exerts when applied systemically to rodents or when applied in vitro to pancreatic β-cells and adipocytes. Due to the common limitations associated with complex model organisms, we then summarize how yeast as a very simple model organism can help to gain valuable comprehensive information on general defence pathways cells exert in response to MG stress. Pioneering studies in additional rather simple eukaryotic model organisms suggest that many cellular reactions in response to MG are highly conserved throughout evolution.

Key words

Diabetes - Oxidative stress - Protein kinases - Methylglyoxal

Full Text

References

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