The results suggest the following molecular etiopathophysiology of DN: (i) hyperglycemia upregulates IGF2, which initiates PTEN, a regulator of IGF2 signaling; (ii) loss of this IGF2-PTEN feedback loop causes changes that are characteristic of DN; and (iii) lowered expression of the repair modulator SPARC results in the development and/or progression of DN.
Insulin-like growth factor (IGF) gene expression is reduced in neural tissues and liver from rats with non-insulin-dependent diabetes mellitus, and IGF treatment ameliorates diabetic neuropathy.