Zinc, type 2 diabetes, diabetic kidney disease: focus on hypoxia.

The incidence of type 2 diabetes mellitus is approaching pandemic levels, posing a major global healthcare problem. Diabetic kidney disease (DKD) is the main cause of the chronic kidney disease. Hyperglycemia-dependent renal hypoxia drives the onset and progression of DKD. The adaptive cellular response to hypoxia depends on the zinc signalling, which promotes expression of the hypoxia-inducible factor-1α (HIF-1α). Zinc is further relevant for anti-inflammatory, antioxidant, anti-apoptotic, and anti-fibrotic signalling pathways with nephroprotective effects in DKD. In this review, we focus on the role of zinc homeostasis in the development of diabetes and DKD, with particular emphasis on hypoxia as the central trigger of DKD. We also discuss the role of the zinc signaling in the cellular and systemic carbohydrate metabolism in the context of diabetes and DKD.