Saturated fatty acids induce insulin resistance in podocytes through inhibition of IRS1 via activation of both IKKβ and mTORC1.

ABSTRACT: Diabetic nephropathy (DN), a microvascular complication of diabetes, is the leading cause of end-stage renal disease worldwide. Multiple studies have shown that podocyte dysfunction is a central event in the progression of the disease. Beside chronic hyperglycemia, dyslipidemia can induce insulin resistance and dysfunction in podocytes. However, the exact mechanisms of free fatty acid (FFA)-induced podocyte insulin unresponsiveness are poorly understood. We used a type 2 diabetic mouse model (db/db) and mouse podocytes exposed to palmitic acid for 24 h followed by an insulin stimulation. Renal function and pathology were evaluated at 25 weeks of age to confirm the DN development. Our results demonstrate that saturated FFA activated the serine/threonine kinases IκB kinase (IKK)β/IκBα and mT

SUBMITTER: Denhez B 

PROVIDER: S-EPMC7728775 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature