The role of iron in development of peripheral diabetic neuropathy in type 2 diabetic, obese, db/db mice.
funded by Deutsche Diabetes Gesellschaft (DDG) 934300-002
Peripheral neuropathy is a serious complication observed in obesity and type 2 diabetes mellitus (T2D). The pathophysiology of this obesity- and diabetes-associated neurological disorder (PDN) includes metabolic, vascular and inflammatory mechanisms but a unifying hypothesis of the culprit pathogenic factors is a matter of debate. Till now, there is no casual therapy against PDN. Our current project is based on previous investigations and preliminary studies which have shown enhanced inflammation as well as electrophysiological and morphological changes in peripheral nerves of animals with obesity and/or type 2 diabetes mellitus. Recently, we have shown a correlation between degree of this disorders and dietary iron concentrations (Fig.1 and 2). In contrast to previous hypotheses suggesting that iron excess might be the most critical pathogenic cofactor, we found a functionally relevant, increase in distal peripheral nerve pathology with chronic iron depletion rather than iron overload which had little effects. Our current project focuses on the identification of the role of iron and nerve inflammation in development of PDN in animal models of obesity and metabolic syndrome (ob/ob mice) as well as obesity and T2D (db/db mice). The identification of metabolic and inflammatory mechanisms of PDN should lead to new therapeutic strategies.