Insulin-like growth factor-binding protein-3 proteolysis is induced after elective surgery

Area of Science:

• Endocrinology
• Proteomics
• Surgical Metabolism

Background:

• Insulin-like growth factors (IGFs) are regulated by IGF binding proteins (IGFBPs).
• Catabolic conditions, such as surgery, can alter IGF and IGFBP levels.
• The specific changes in IGFBPs after surgery and their functional implications remain unclear.

Purpose of the Study:

• To investigate the changes in insulin-like growth factor-I (IGF-I) and IGF binding protein (IGFBP) levels following cholecystectomy.
• To identify the specific IGFBPs affected by surgery and characterize any proteolytic activity in postoperative serum.

Main Methods:

• Serum samples were collected from 16 patients before and after cholecystectomy.
• IGF-I levels were measured in extracted and unextracted samples.
• IGFBP levels (IGFBP-3, IGFBP-2, 24 kDa IGFBP) were assessed using ligand blot and immunoblot techniques.
• Proteolytic activity in postoperative serum was analyzed through coincubation assays and inhibition studies with various protease inhibitors.

Main Results:

• Unextracted IGF-I levels increased approximately 3-fold postoperatively, while extracted IGF-I showed no significant change.
• IGFBP-3 levels decreased by 36% postoperatively, with a significant reduction in intact IGFBP-3 (84.2%) and an increase in a 31 kDa IGFBP-3 fragment (57.5%).
• Postoperative serum exhibited proteolytic activity against IGFBP-3, inhibited by a specific set of protease inhibitors, suggesting a metal-dependent trypsin-like serine protease.

Conclusions:

• Surgery induces significant alterations in IGFBP-3, characterized by decreased intact levels and increased proteolytic fragments.
• The identified proteolytic activity in postoperative serum may play a role in modulating IGF-I bioavailability.
• Proteolysis of IGFBP-3 is a potential mechanism to counteract the catabolic state following surgery, possibly by influencing IGF-I tissue uptake.