Human Islet Research Network
Menu

Project Abstracts - CBDS

Development of an Early Diagnostic Biomarker and Novel Treatment Strategy for T1D

Contact PI: Anath Shalev, MD, University of Alabama at Birmingham (U01 DK120379)

 

Summary of Project Abstract & Publications

Start Date: September 15, 2018

 

Abstract

Loss of insulin producing beta cells is a major problem of type 1 diabetes (T1D) and neither therapies that target this process nor simple measures/biomarkers that quantify it are currently available in humans. We recently discovered thioredoxin-interacting protein (TXNIP) as an attractive target in this regard, since genetic or pharmacological TXNIP downregulation with verapamil reduced beta cell apoptosis, increased pancreatic beta cell mass, and protected against and even reversed diabetes in mice. Now our, randomized, double-blind, placebo-controlled trial revealed that oral verapamil added for 12 months to a standard insulin regimen in adult subjects with recent onset T1D improved mixed meal-stimulated C-peptide area under the curve as a measure of the body’s own beta cell function. We further discovered that a specific TXNIP-induced small non-coding RNA (microRNA) is not only the most highly enriched microRNA in human beta cells, but is also released from dying beta cells, detectable in mouse and human serum, increased in T1D, and inversely correlated with remaining beta cell function. We therefore hypothesize that TXNIP inhibition provides a novel treatment strategy for T1D and that this TXNIP-induced serum microRNA represents an early diagnostic biomarker for T1D-associated beta cell loss in humans. Using different models of diabetes, human islets and pre-collected serum at various stages of T1D, we will now test this hypothesis. The proposed studies will thereby help develop a novel tool for the early diagnosis and treatment of T1D.

 

Meet the Grant Team

  Leadership
           
         

Anath Shalev, MD

Investigator
University of Alabama at Birmingham

         
  Research Staff

Guanlan Xu, PhD

University of Alabama at Birmingham

 

Gu Jing, PhD

University of Alabama at Birmingham