The Role of PPARgamma ligands in neuroprotection following cerebral ischemia

Sophia Sundararajan, MD, PhD
Case Western Reserve University

Lay Abstract

Thiazolidinediones are drugs that are taken by patients to improve blood glucose in the treatment of Type 2 diabetes and target PPARgamma (peroxisome proliferator-activated receptor gamma). These drugs have recently been found to reduce inflammation in a variety of diseases. Inflammation is a component of stroke and inflammatory gene expression can increase stroke size. Dr. Sundararajan’s lab has found that PPARgamma expression is increased after stroke and rats treated with thiazolidinediones have smaller strokes and less inflammatory gene expression. In addition, they suggest that thiazolidinediones work best when given when the blood vessel is still blocked and not after it has been reopened. They will 1) test the ability of mice lacking PPARgamma to respond to thiazolidinediones, 2) evaluate how gene expression is altered by thiazolidinediones both in the mice lacking PPARgamma and mice with normal PPARgamma expression, and 3) examine the sequence of events which occur following stroke in both to understand the mechanisms by which thiazolidinediones protect the brain from stoke. Understanding these drugs as potential therapy for stroke will also help make the best decisions regarding which anti-diabetic drug might benefit individual patients with Type 2 diabetes.

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ß-Cell failure and the development of non insulin-dependent diabetes mellitus: Role of impaired insulin and IGF-1 signaling in ß-cell dysfunction

Nadia Rachdaoui, PhD
Case Western Reserve University

Lay Abstract

Dr. Rachdaoui has proposed experiments to study what brings about dysfunction and death to the pancreas. Specifically, she will study 1) how high blood insulin that is observed in obesity negatively influences the ability of the pancreas to make insulin, and 2) how high blood insulin associated with high blood sugar could further accelerate pancreatic deterioration and lead to the development of Type 2 diabetes. If these experiments can determine the basic mechanisms that explain how the pancreas becomes “exhausted” in some patients, but not in others, it may provide new information about how to prevent failure of the pancreas.

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Gene Expression Profile of White Adipose Tissue During Pregnancy and Diabetes

Sylvie Hauguel-de Mouzon, Ph.D.
Director, Molecular Research Division
MetroHealth Medical Center
Department of Reproductive Biology

Lay Abstract

Dr. Hauguel-de Mouzon will investigate the mechanisms of insulin resistance in pregnant diabetic women by examining the genes in the mothers’ fat cells. Comparisons will also be made with the genes expressed in their placenta to identify the metabolic processes that are modified by pregnancy and diabetes. This will allow to explore why babies of diabetic and obese mothers have an increased risk for obesity at birth as well as for developing diabetes later in life.

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