rebecca-autenried@uiowa.edu
Mentor: E. Dale Abel, M.D./Ph.D.
Lab Room: 4310 PBDB
Lab Phone: 319-335-7962

The role of insulin receptor substrate complexes in cardiac hypertrophy

Diabetes is a growing global epidemic, with 37 million people living with the disease in North America and 382 million living with the disease worldwide. This is a serious problem because complications of type II diabetes are costly to the individual and to the system, leading to stroke, retinopathy, nephropathy, neuropathy, foot ulcers (often requiring amputation), and heart disease. Because 8/10 individuals with diabetes die from macrovascular cardiovascular events such as ischemic heart disease, stroke and heart failure, our lab focuses on molecular mechanisms for macrovascular complications of diabetes.

The Abel lab has discovered that insulin signaling worsens cardiac pressure overload hypertrophy via a series of signaling proteins downstream of the insulin receptor (IR) present within the plasma membrane of the cardiomyocyte. IR acts through phosphorylating insulin receptor substrate 1 (IRS1) and insulin receptor substrate 2 (IRS2) which then form complexes with other signaling proteins, including but not limited to: p85, p110, Grb2, SOS, Ras, and Shc. These complexes activate PI(3)K, Akt, and the MAP kinase pathways to regulate intracellular glucose metabolism, glycogen/lipid/protein synthesis, specific and general gene expression, and cell growth and differentiation. Certain signal transduction pathways that promote abnormal cellular growth responses in adult cardiomyocytes leads to a pathological cardiac hypertrophic response.

Previous work in our lab, by Drs Riehle and Weatherford, has started to elucidate the specific roles of IRS1 and IRS2 in the heart. My work in the Abel lab will focus on identifying IRS1 and IRS2 binding partners that are specific to the heart. These IRS-mediated protein interactions may provide us with therapeutic target candidates to prevent the development of hypertrophic cardiomyopathy in patients with type II diabetes.