Relevance of insulin-like growth factor 2 in the etiopathophysiology of diabetic nephropathy: Possible roles of phosphatase and tensin homolog on chromosome 10 and secreted protein acidic and rich in cysteine as regulators of repair

摘要: Background:  Diabetic nephropathy (DN) is a devastating complication of diabetes, the exact molecular pathophysiology which not well established. Hyperglycemia increases insulin-like growth factors (IGFs), especially IGF2, acts via IGF1 receptor present on renal cells. Elevated glucose levels damage kidney, repaired by modulators such as secreted protein acidic and rich in cysteine (SPARC). Hence, it was hypothesized that IGF2 SPARC may have an important role etiology DN. Methods:  Human biopsies, histopathologically categorized normal, early Type 2 diabetes mellitus (T2DM), or established DN, were analyzed for localization expression its negative regulator phosphatase tensin homolog chromosome 10 (PTEN), SPARC. Results:  Expression PTEN, increased biopsies from T2DM patients compared with normal samples. Although DN patients, PTEN decreased. Real-time reverse transcription–polymerase chain reaction indicated transcript greater than those β-actin all human biopsy samples. Conclusion:  The results suggest following etiopathophysiology DN: (i) hyperglycemia upregulates initiates signaling; (ii) loss this IGF2–PTEN feedback loop causes changes are characteristic DN; (iii) lowered repair modulator development and/or progression DN. targeting relevant modulators, like SPARC, be management