Regulation of PDH activity by MG and the impact on diabetes complications (A03)

• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: from 2014 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 236360313

Methylglyoxal (MG) is a highly reactive metabolite that forms adducts on proteins, leading to protein dysfunction. In the previous funding period, we found that elevated MG levels lead to reduced activity of a key metabolic enzyme, Pyruvate Dehydrogenase (PDH), via a novel unknown mechanism. MG levels are elevated in diabetic patients. Furthermore, diabetic patients are known to have reduced PDH activity, although the mechanism is not completely understood. We aim to combine these observations, to understand mechanistically how MG regulates PDH activity, and whether this is happening in diabetic patients.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1118: Reactive metabolites as a cause of diabetes complications
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Head: Professor Dr. Aurelio A. Teleman