13^th Annual Henry L. Brasza Lecture in Diabetes

Wednesday, April 7, 2021 at 1:00 p.m.

Via Zoom: https://wayne-edu.zoom.us/j/92129691917?pwd=MHp4Z2xtaTVPcWdsZGdpMkFMMnlLQT09

Meeting ID: 921 2969 1917                           Passcode: 550546

Domenico Accili, MD

Professor of Medicine at Columbia University and Director of the Columbia University Diabetes and Endocrinology Research Center

“The new Biology of Diabetes”

Abstract

Insulin resistance and pancreatic b cell failure are the key pathogenic factors in type 2 diabetes. We have previously demonstrated a role of β cell dedifferentiation in b cell dysfunction. However, in order to design new treatments for this condition, we need to identify key mediators of this process. To this end, we undertook an integrated approach in which we examined gene expression and genome-wide chromatin changes associated with the onset of diabetes. The integration of gene expression and genome-wide histone modification profiles indicates that β cell dysfunction can be explained by a relatively small subset of genes. I will discuss how this small number of genes can cause a global failure to adapt to physiologic stressors, with increased repression of gene expression and failure to activate stress-response programs. We show that as β cells fail, they become more similar to immature progenitor cells and activate α cell-specific genes. We tested the idea that β cell failure entails a progressive acquisition of α cell features. I will illustrate results from human islet single cell RNA sequencing that support this hypothesis to propose a new mechanism of β cell failure.