The current focus of Dr. Wang’s lab is to understand the functional roles of peroxisome proliferator-activated receptors (PPARs) in normal physiology and metabolic diseases in a variety of metabolically active tissues and the molecular mechanisms of their action, and to investigate their interactions with environmental factors and other signaling events.  PPARs are nuclear receptors (NRs) that control many cellular and metabolic processes. 

Dr. Yong-Xu Wang came to the Program in Gene Function and Expression and the Program of Molecular Medicine at UMMS after completing his PhD at the University of Iowa followed by post doctoral activities at the Salk Institute in La Jolla, California.

The Research:  Regulation of Insulin Secretion and Glucose Metabolism by ß Cell-Specific PPAR

Obesity is the single most important contributor to the cause of type 2 diabetes which is characterized by insulin resistance and pancreatic beta (ß) cell dysfunction.  However, overt diabetes develops only when ß cells fail to compensate for the increased demand for insulin.  It is recognized that elevated fatty acid levels and triglycerides in ß cells impair insulin secretion and may ultimately cause the ß cells to fail, but it is not understood why. The key molecular components in the ß cells that control fatty acid metabolism remain to be identified.

Recently, PPAR , a member of PPAR subfamily has shown to be a major transcriptional regulator for fatty acid oxidation and oxidative metabolism in fat and skeletal muscle.  PPAR is abundantly expressed in the islets, which are endocrine cells in the pancreas responsible for secreting insulin.  However, the PPAR, functional role in this tissue is completely unknown.

Islet PPAR may play an important part in maintaining ß cell function, particularly in obese individuals.  Dr. Wang is testing this hypothesis using ß cell-specific PPAR knockout mice. Knockout mice, genetically engineered mice in which one or more genes have been "turned off" through a gene knockout, are important animal models for studying the role of genes whose functions are unknown.  By causing a specific gene to be “turned off” in the mice and observing any change in normal conditions or behaviors, researchers like Dr. Wang can infer its probable function.

The mice are being fed either a regular chow diet or a high-fat diet.  The first goal of his research is to examine islet metabolism, morphology and insulin secretion.  Secondly, Dr. Wang hopes to determine the effects of loss of PPAR on whole body glucose homeostasis,

“Our focus is to understand the transcriptional pathways controlling energy metabolism and how dysregulation of these pathways might lead to insulin resistance and diabetes.  We hope that these studies may provide molecular insights into the cause of obesity-associated type 2 diabetes.”