Projects and Grants per year
Grants and Contracts Details
Description
Abstract
Type 2 diabetes (T2D) is a metabolic disorder affecting 463 million people in the Unites
States1.T2D is characterized primarily by hyperglycemia and inflammation driven insulin
resistance2. Hyperglycemia leads to generation of reactive oxygen species (ROS) and
oxidative stress in the mitochondria3. ROS also causes endoplasmic reticulum (ER) stress4.
There is a tight interconnection between the ER and mitochondria stress through
mitochondrial-associated membranes (MAMs) that fuel a vicious cycle of stress-mediated
organelle dysfunction. MAMs orchestrate the protein folding and calcium buffering that in turn
affect organelle homeostasis and cellular signaling pathways to control cell and organismal
metabolism5,6. These findings imply a role of altered MAM and inflammatory mechanisms
underlying insulin resistance in the development of diabetes, yet a large gap exists in how
inflammation influences the structure, signaling, and functions of MAMs in diabetes remains
elusive. Therefore, we hypothesize that inflammation induced changes in MAMs further
promote inflammatory profiles and additionally impair calcium shuttling between ER and
mitochondria in PBMCs. We propose the following specific aims to investigate mechanisms
underlying chronic inflammation exacerbated diabetes by investigating changes in the MAMs
in the immune cells from T2D subjects. Defining mechanisms driving T cell inflammation will
significantly enhance our current appreciation of inflammation towards the goal of improving
life span. The long-term goal of this project is to identify specific mechanisms that regulate
the MAM structure and function, that cans serve as drug target for prevention and/or treatment
strategies in T2D.
Status | Finished |
---|---|
Effective start/end date | 2/23/13 → 11/30/22 |
Funding
- Washington University in St. Louis
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.
Projects
- 1 Finished
-
University of Kentucky Pilot and Feasibility Research Program
Kern, P. (PI)
Washington University in St. Louis
2/23/13 → 11/30/23
Project: Research project