The role of insulin-like growth factors in diabetic kidney disease.
Early renal manifestations of type I diabetes include kidney enlargement, increased glomerular filtration rate, and renal plasma flow. These hemodynamic changes may be caused by a number of factors, including growth hormone and/or insulin-like growth factor-I (IGF-I). Streptozotocin-induced insulinopenic diabetes in rats represents a model of human type I diabetes and is associated with the early hemodynamic changes in the kidney seen in poorly controlled type I diabetic patients. These changes are preceded by an accumulation of IGF-I peptide in the kidney. Insulin-like growth factor-I is not locally produced, but rather accumulates from circulating IGF-I, trapped by increased levels of IGF-binding proteins, particularly IGF-binding protein-1. The hemodynamic effects, reproduced by infusions of recombinant human IGF-I in normal rats, may be blocked by co-infusion of a kinin-receptor antagonist, suggesting that at least one of the mechanisms involved is the kallikrein-kinin system. These studies strongly support the notion that the IGF system may play a role in early hemodynamic manifestations of the diabetic kidney. Whether these effects lead to long-term diabetic renal disease remains to be studied.
LeRoith
D
D
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Werner
H
H
Phillip
M
M
Roberts
C T
CT
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D013002:Somatomedins / Q000502:physiology*
D013002:Somatomedins