According to current figures, one in ten adults has diabetes and an equally large number has the precursor to it, prediabetes. Diabetes is the leading cause of blindness, chronic kidney failure, heart attack, stroke and leg amputations. These diabetic complications often determine the mortality of patients with diabetes. Diabetic complications are evident in subtypes of diabetes as early as the manifestation of the disease itself. However, no therapeutic approaches are currently available that specifically target intracellular metabolic pathways underlying the development of diabetic complications. In addition, it is still not possible to reliably determine the risk of late onset diabetes or to induce remission of established late complications.

The SFB1118 aims to understand diabetes complications by studying the intracellular effects of reactive metabolites (RM), such as reactive oxygen species (ROS), dicarbonyls (DC), or glucose metabolites (O-Glc-NAc), which are generated during energy metabolism.

Our previous work identified novel molecular pathomechanisms of diabetic complications as well as specific targets of RM in the development of insulin resistance, retinopathy, sensory and autonomic neuropathy, nephropathy, and diabetic cardiopathy.

Paradigm-shifting findings of this SFB demonstrated that synergistic enzyme systems and autoregulatory feedback loops determine the accumulation of RM. RM induce post-translational modifications of proteins and DNA with functional changes that are followed by cellular compensatory mechanisms, insulin resistance, DNA damage and/or senescence and can lead to tissue fibrosis and organ failure (multiple-hit concept).
The overall goal is to achieve long-term targets for prevention and remission of existing late complications in diabetes.

Reactive metabolites (RM) from various sources accumulate through increased production or reduced detoxification, in obesity and/or (pre)diabetes. RM contribute to the inhibition of insulin signalling by lipids and amino acids. Post-translational modification of proteins and DNA resulting from RM, initiates the transition from healthy to chronically impaired metabolism, resulting in DNA damage and a cellular adaptation to metabolic stress. In respect to a multi-hit concept, this culminative damage can be viewed as being equivalent to subclinical inflammation. Depending on the subtype of diabetes and gender, different cellular protective mechanisms can prevent organ damage. However, when lost or impaired, the damage which can occur ultimately leads to fibrosis and loss of organ function, in high-risk patients. Potential therapeutic interventions which interrupt and inhibit this cascade been identified using in vitro and in vivo genetic models and their relevance in humans will be tested further through the use of induced pluripotent stem cells. The association of RM induced effects with diabetes associated damage, as well as the potential for such effects to be mitigated by targeted interventions will be investigated in prospective cohorts of different subtypes of diabetes. Gender-specific parameters will be included in all steps of translation, as well as in transfer to teaching and clinical settings. The aim of this consortium is to develop new, tailored concepts for the prevention and therapy of RM-induced diabetes damage.
AGEs, advanced glycation endproducts; IPS, induced pluripotent cells, RM, reactive metabolites; ROS, reactive oxygen species.

Prof. Dr. Aurelio Teleman

Prof. Dr. Aurelio Teleman wurde in die renommierte European Molecular Biology Organisation (EMBO) aufgenommen

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Prof. Dr. Dr. h.c. Peter Nawroth

Prof. Dr. Dr. h.c. Peter Nawroth erhielt renommierten Camillo Golgi Preis

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Prof. Dr. Hans-Peter Hammes

Camillo Golgi-Preis für Prof. Dr. Hans-Peter Hammes 

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Warum Diabetes mehr als Zucker ist

SFB 1118 - Reaktive Metabolite als Ursache diabetischer Folgeschäden

Sprecher: Prof. Dr. Stephan Herzig

Referenten: Prof. Dr. Stephan Herzig, Dr.…

Diabetes – alles eine Frage der Enzyme?

SFB 1118 – Reaktive Metabolite als Ursache diabetischer Folgeschäden

Sprecherin: Verena Peters

Moderation: Sebastian Riemer, Rhein-Neckar-Zeitung