Linagliptin Limits High Glucose Induced Conversion of Latent to Active TGFß through Interaction with CIM6PR and Limits Renal Tubulointerstitial Fibronectin.

ABSTRACT:

Background

In addition to lowering blood glucose in patients with type 2 diabetes mellitus, dipeptidyl peptidase 4 (DPP4) inhibitors have been shown to be antifibrotic. We have previously shown that cation independent mannose-6-phosphate receptor (CIM6PR) facilitates the conversion of latent to active transforming growth factor β1 (GFß1) in renal proximal tubular cells (PTCs) and linagliptin (a DPP4 inhibitor) reduced this conversion with downstream reduction in fibronectin transcription.

Objective

We wanted to demonstrate that linagliptin reduces high glucose induced interaction between membrane bound DPP4 and CIM6PR in vitro and demonstrate reduction in active TGFß mediated downstream effects in a rodent model of type 1 diabetic nephropathy independent of high glycaemic le

SUBMITTER: Gangadharan Komala M 

PROVIDER: S-EPMC4624988 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature