Format

Send to

Choose Destination
Cell Metab. 2018 Apr 3;27(4):926-934.e8. doi: 10.1016/j.cmet.2018.02.003. Epub 2018 Mar 15.

Elevated Levels of the Reactive Metabolite Methylglyoxal Recapitulate Progression of Type 2 Diabetes.

Author information

1
German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg University, 69120 Heidelberg, Germany.
2
German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg University, 69120 Heidelberg, Germany; Department of Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, 69120 Heidelberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Helmholtz-Zentrum, 85764 Munich, Germany.
3
Department of Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, 69120 Heidelberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Helmholtz-Zentrum, 85764 Munich, Germany.
4
German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
5
German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg University, 69120 Heidelberg, Germany. Electronic address: a.teleman@dkfz.de.

Abstract

The molecular causes of type 2 diabetes (T2D) are not well understood. Both type 1 diabetes (T1D) and T2D are characterized by impaired insulin signaling and hyperglycemia. From analogy to T1D, insulin resistance and hyperglycemia are thought to also play causal roles in T2D. Recent clinical studies, however, found that T2D patients treated to maintain glycemia below the diabetes definition threshold (HbA1c < 6.5%) still develop diabetic complications. This suggests additional insulin- and glucose-independent mechanisms could be involved in T2D progression and/or initiation. T2D patients have elevated levels of the metabolite methylglyoxal (MG). We show here, using Drosophila glyoxalase 1 knockouts, that animals with elevated methylglyoxal recapitulate several core aspects of T2D: insulin resistance, obesity, and hyperglycemia. Thus elevated MG could constitute one root cause of T2D, suggesting that the molecular causes of elevated MG warrant further study.

KEYWORDS:

Drosophila; Glo1; methylglyoxal

PMID:
29551588
DOI:
10.1016/j.cmet.2018.02.003
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center