Objective:

To investigate whether increased IGFBP-1 following Roux-en-Y gastric bypass (RYGB) surgery is associated with upregulation of IRS-1 and its downstream PI3K/AKT/GSK-3β signaling components.

Approach:

• Animal Model: Wild-type C57BL/6 mice and IGFBP-1 knockout mice were used, along with an induced diabetes model.
• Measurements: Body weight, fasting blood glucose, and HOMA-IR were assessed preoperatively and at 1 to 8 weeks postoperatively.
• Biochemical Analysis: Plasma samples were analyzed for IGFBP-1, IRS-1, PI3K, AKT, and GSK-3β using ELISA and real-time PCR.

Key Findings:

• Body weight, fasting blood glucose, and HOMA-IR improved significantly after RYGB.
• IGFBP-1 levels were significantly elevated post-surgery in wild-type mice.
• Marked upregulation of IRS-1, PI3K, and AKT, and downregulation of GSK-3β were observed in wild-type mice, but these changes were absent in knockout mice.
• RYGB reversed multi-organ pathological changes in wild-type mice, including cardiomyocyte hypertrophy, hepatic steatosis, glomerular enlargement, and adipocyte hypertrophy, but only partially in knockout mice.

Interpretation:

Elevated IGFBP-1 is associated with improved insulin sensitivity and upregulation of the IRS/PI3K/AKT/GSK-3β signaling axis after RYGB.

Limitations:

• The study was conducted in a mouse model, which may not fully replicate human physiology.
• Further investigation is required to elucidate the specific mechanisms by which IGFBP-1 influences metabolic recovery.

Conclusion:

IGFBP-1 is associated with the normalization of glucose homeostasis and multi-tissue repair after RYGB.