Berberine improves kidney function in diabetic mice via AMPK activation.

Area of Science:

• Nephrology
• Metabolic Diseases
• Pharmacology

Background:

• Diabetic nephropathy is a leading cause of death in diabetic patients.
• Effective therapies are needed to prevent diabetic nephropathy.
• The precise molecular mechanisms of berberine (BBR) in diabetic kidney disease are not fully understood.

Purpose of the Study:

• To investigate the molecular mechanism of BBR in improving kidney function in diabetic nephropathy.
• To determine the role of AMP-activated protein kinase (AMPK) in BBR's renoprotective effects.

Main Methods:

• In vitro studies using human glomerulus mesangial cells (HGMCs) exposed to high glucose (HG) and BBR.
• In vivo studies using streptozotocin-induced diabetic mice, including wildtype and AMPKα2-deficient models.
• Assessed AMPK activation, oxidative stress (ROS), serum BUN, creatinine clearance (Ccr), urinary protein excretion, and glomerular morphology.

Main Results:

• BBR activated AMPK in HGMCs by increasing phosphorylation and activity, an effect dependent on LKB1.
• BBR mitigated HG-induced oxidative stress in HGMCs, an effect dependent on AMPK activation.
• In vivo, BBR improved kidney function and reduced glomerulosclerosis in wildtype diabetic mice but not in AMPKα2-deficient mice.

Conclusions:

• AMPK activation is essential for the renoprotective effects of BBR in diabetic nephropathy.
• BBR demonstrates therapeutic potential for diabetic kidney disease through AMPK activation.
• Targeting the AMPK pathway may offer a novel strategy for treating diabetic complications.