The involvement of growth hormone (GH), insulin-like growth factors (IGFs) and vascular endothelial growth factor (VEGF) in diabetic kidney disease.
At present, diabetic kidney disease affects about 15-25 % of patients with type 1 diabetes (T1D) and 30-40 % of patients with type 2 diabetes (T2D). Several decades of extensive research have elucidated various pathways to be implicated in the development of diabetic kidney disease. These include metabolic factors beyond blood glucose (e.g. advanced glycation endproducts (AGEs)), haemodynamic factors (e.g. the renin angiotensin system (RAS)), intracellular signaling molecule proteins (e.g. protein kinase C (PKC)) and growth factors/cytokines (e.g. growth hormone (GH), insulin-like growth factors (IGFs), transforming growth factor beta (TGF-beta) and vascular endothelial growth factor (VEGF)). This review focuses on the role of three of these growth factors, i.e. GH, IGFs and VEGF. A brief discussion of each system is followed by description of its expression in the normal kidney. Then, for each system, in vitro, experimental and clinical evidence addressing the role of the system in diabetic kidney disease is presented. The interplay of each system to other potential pathways will also be addressed. Finally, well-known and potential therapeutic strategies targeting the GH/IGF and VEGF systems in a specific or indirect way will discussed.
Flyvbjerg
Allan
A
Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital, DK-8000 Aarhus C, Denmark. allan.flyvbjerg@dadlnet.dk
Khatir
Dinah S
DS
Jensen
Louise J N
LJ
Dagnaes-Hansen
Frederik
F
Gronbaek
Henning
H
Rasch
Ruth
R
D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000503:physiopathology*; D019382:Human Growth Hormone / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000502:physiology / Q000503:physiopathology; D013002:Somatomedins / Q000187:drug effects / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*
D013002:Somatomedins; D042461:Vascular Endothelial Growth Factor A; D019382:Human Growth Hormone