Mission Statement

The Center for Metabolic Biology at Arizona State University is a transdisciplinary, multi-investigator Center designed to define the molecular, biochemical, and cellular defects responsible for insulin resistance and type 2 diabetes mellitus and to translate these findings to the patient bedside by means of patient-oriented research. Center faculty members come from the School of Life Sciences, the Department of Kinesiology, and the Department of Chemistry and Biochemistry. Center investigators perform research into the basic molecular, cellular, and physiological mechanisms responsible for insulin resistance and type 2 diabetes and then translate the basic hypotheses that arise from these experiments into clinical research in small groups of subjects with insulin resistance and diabetes. The unique aspect of the Center for Metabolic Biology is that we provide the translational component for basic researchers in a collaborative environment with physician scientists on our faculty. The Center’s laboratories are housed in approximately 13,000 square feet of laboratories in the Interdisciplinary Science and Technology Building 1 on the Arizona State University Tempe Campus. Our patient-oriented research is performed at both the Carl T. Hayden VA Medical Center and a newly developed Clinical Research Center in the Department of Kinesiology at Arizona State University.

The kind of research currently performed in the Center is exemplified by the following. It is widely believed that insulin resistance is the underlying precursor for type 2 diabetes mellitus. One project in the Center focuses on the role of Insulin Receptor Substrate (IRS)-1 in skeletal muscle in insulin resistance. IRS-1 is a central molecule in the insulin signaling cascade. It is tyrosine phosphorylated by the insulin receptor tyrosine kinase and transmits the insulin signal downstream to its target effectors of glucose and fat metabolism and gene expression. IRS-1 function is strongly modulated, in addition, by phosphorylation of serine and threonine amino acid residues in its sequence. Many of these phosphorylation sites act in a complex and poorly understood concerted fashion to tune the activity of this protein. Very little is known about these processes in muscle from insulin resistant subjects. Center scientists are engaged in experiments to discover these serine and threonine phosphorylation sites using a combined in vitro and in cell mass spectrometry based approach, and then to define the function of these sites. We then are using the knowledge gained about these sites to target their identification and quantification in IRS-1 obtained from small, percutaneous biopsies of human muscle. These muscle biopsies are obtained from healthy volunteers and type 2 diabetic patients during a procedure called a euglycemic clamp, whereby the subject’s muscle can be exposed to insulin in vivo while at the same time maintaining euglycemia by means of an exogenous glucose infusion.

Although the mission of the Center for Metabolic Biology does not include such endeavors as pharmaceutical development, it is clear that studies such as that described above have the strong potential for both testing drugs that are believed to improve insulin sensitivity by unknown mechanisms as well as identifying new targets for highly specific pharmaceutical agents designed to treat insulin resistance. Such studies often require larger-scale trials than our current resources allow. Development of additional resources that would facilitate the translation of our very basic findings not only to patient-oriented research, but eventually to treatment of type 2 diabetes mellitus and insulin resistance in general would be invaluable resources, and complete the “bench-to-bedside” (and back) loop.

Finally, one of the major public health challenges of the Twenty First Century will be how to reduce the growing epidemic of obesity, type 2 diabetes mellitus, and cardiovascular disease. All of these diseases have insulin resistance at their molecular basis, so public interventions that reduce insulin resistance, such as physical activity and a healthy, calorie-limited diet are desperately needed. This is especially true in Border States such as Arizona. The prevalence of insulin resistance and type 2 diabetes mellitus is especially high in Native and Mexican American groups, and Arizona’s high percentage of these ethnic groups makes it especially critical from a public health perspective. Enhancement of resources to deliver our knowledge of the pathophysiology of insulin resistance to institutions with the resources and mission to affect public is a critical need for the state and region.