The growth hormone/insulin-like growth factor axis and the development of diabetic nephropathy in animal models of juvenile (type 1) diabetes: A review

Diabetic nephropathy (DN) is the most common and severe complication of diabetes mellitus (DM), characterized by an early increase in kidney size, followed by albuminuria and progressive azotemia. The importance of growth hormone (GH) and insulin-like growth factor I (IGF-I) in mediating renal changes seen in DN has been well established in several animal models. The NOD mouse is a model of spontaneous diabetes, which develops significant glomerular lesions, including the development of significant albuminuria and an increase in mesangial sclerosis, similar to human disease. In previous studies we were able to show that renal hypertrophy of diabetic NOD mice is associated with an increase in renal extractable IGF-I protein. In situ hybridization studies revealed a decrease in cortical IGF-I and an increase in cortical IGFBP1 mRNA abundance. These changes persisted even after 4 weeks of diabetes and could be reverted with insulin therapy. We have also found that serum GH levels are increased at one month of diabetes, mimicking human disease, in contrary to previous descriptions using the STZ model. These changes in the GH-IGF system in the NOD model, described by us, suggest a major role for these growth factors in the development of DN.