Targeting the Complications of Metabolic Syndrome: Diabetes and Inflammation

Organizers: Loretta Bober, Schering-Plough Research Institute and Judith L. Treadway, Pfizer Inc

The prevalence of obesity in the United States has led to a significant increase in the complications associated with metabolic syndrome, including diabetes. While many therapeutic approaches target appetite to address this problem, an increasing body of data has demonstrated that many of these complications can be linked to a disregulation of the body's immune system associated with this syndrome. In this symposium, we will investigate the role of the inflammatory mediators in the problems of metabolic syndrome. These approaches will ultimately lead to improved therapeutic targets to combat this medical need.

Program:

1:00-1:10 PM: Introduction
Judith L. Treadway, Pfizer Inc

1:15-1:55 PM:
Alexander S. Banks, College of Physicians and Surgeons, Columbia University
"Cytokine Action in Insulin Resistance: The Role of SOCS Proteins"

2:00-2:40 PM:
Anthony W. Ferrante, Naomi Berrie Diabetes Center, Columbia University
"Obesity, Inflammation and Macrophages: Role of Chemokines in Macrophage Accumulation in Adipose Tissue"

2:45-3:15 PM: Coffee Break

3:20-4:00 PM:
Richard A. Cohen, Boston University School of Medicine
"Oxidant-induced Protein Modifications in Diabetes and Metabolic Syndrome"

4:05-4:45 PM:
Michael J. Quon, Diabetes Unit, Lab of Clinical Investigation, NIH
"Inflammatory Markers and the Metabolic Syndrome"

4:50-5:00 PM: Closing Remarks
Loretta Bober, Schering-Plough Research Institute

Abstracts:

Cytokine Action in Insulin Resistance: The Role of SOCS Proteins
Alexander S. Banks, Ph.D.
College of Physicians and Surgeons, Columbia University

Infection, inflammation, obesity and other pathological processes regulate the circulating levels of cytokines. Once at their destination, cytokines bind to a cell-surface receptor, triggering downstream signaling events. The Suppressors of Cytokine Signaling (SOCS) serve to inhibit these signaling events in a classical negative feedback loop. Although initially characterized for their ability to inhibit JAK kinases and STAT activity, SOCS proteins can also down-regulate insulin signaling by modulating the insulin receptor and insulin receptor substrate complex. Mice with genetic ablation of SOCS genes have improved insulin signaling however, this can give rise to unexpected pathological consequences such as hypoglycemia and steatohepatitis. Hence, the increased levels of cytokines in inflammatory states such as infection or obesity can produce insulin resistance in part through induction of SOCS proteins. However, uncontrolled insulin signaling due to SOCS deficiency also produces adverse consequences. Hence, SOCS molecules serve as the cytokine controlled rheostat to regulate insulin signaling.

Obesity, Inflammation and Macrophages: Role of Chemokines in Macrophage Accumulation in Adipose Tissue
Anthony W. Ferrante Jr., M.D., Ph.D.
Naomi Berrie Diabetes Center, Columbia University

Obesity induces an inflammatory response that has been implicated in the development of medically important complications, including atheros