Role of growth hormone, insulin-like growth factors (IGFs) and IGF-binding proteins in the renal complications of diabetes.

This review has updated recent facets of evidence for the significance of the GH/IGF system in the development of diabetic kidney disease. It seems evident, however, that there is still an extensive number of questions that need to be answered before diabetic kidney disease is fully understood. The knowledge we have today indicates that GH/IGF axis, through a complex system comprising GHR, GHBP, IGFs, IGF receptors and IGFBPs may be responsible for both early and late renal changes in experimental diabetes (Fig. 3). In view of the complexity of the GH/IGF system, it will be a challenge to fully characterize the renal effects of GH/IGFs in diabetic kidney disease. There is no doubt that information on this topic will occur with increasing pace in the near future and that a understanding of the above-mentioned mechanisms will allow the further development of existing antagonists and design of new drugs, which may prove to be useful for therapeutic manipulation in the treatment of diabetic nephropathy. The development of long-acting somatostatin analogues and GH antagonists, both with a specific action on the GH/IGF axis, seems to be one important step ahead. The combined administration of one of these antagonists with other drugs with a well described renoprotective action (such as ACE inhibitors) opens an interesting new dimension.