IBRI DIABETES CENTER - WITCZAK LAB
Focus: The molecular and cellular factors that regulate skeletal muscle metabolism during both physiological and pathological conditions.
The Witczak Lab is interested in determining how genetic, nutritional and environmental factors coordinately regulate skeletal muscle substrate uptake and utilization, resulting in differential manifestations of tissue function in both pre-clinical animal models and clinical patient populations. Our overall goal is to identify novel proteins responsible for the regulation of key metabolic processes, such as glucose uptake and protein synthesis, and then utilize that knowledge towards the development of innovative therapies for chronic human disease states such as type 2 diabetes.
Specific scientific areas of focus in the lab include:
Targeting resistance exercise training/mechanical loading-stimulated skeletal muscle glucose uptake for the treatment of type 2 diabetes.
Type 2 diabetes currently afflicts more than 25.8 million Americans creating an economic burden totaling about $245 billion per year. It is a progressive metabolic disease characterized by hyperglycemia, hyperinsulinemia and insulin resistance in skeletal muscle, the primary site of insulin-mediated blood glucose disposal. Importantly, while insulin-stimulated muscle glucose uptake is impaired in type 2 diabetes, the ability of insulin-independent stimuli, such as exercise, to increase muscle glucose uptake and lower blood glucose levels remains intact. Thus, increasing muscle glucose uptake via an exercise-dependent mechanism is an effective strategy to treat hyperglycemia in type 2 diabetes. Despite this fact, the medications currently prescribed for type 2 diabetes target insulin secretion from the pancreas, hepatic glucose output, glucose excretion from the kidneys, glucose absorption from the intestines and insulin sensitivity in adipose tissue. None of the medications currently available target exercise-dependent skeletal muscle glucose uptake. A critical barrier in the development of new type 2 diabetes therapies that target exercise-dependent muscle glucose uptake is identification of the intracellular proteins that govern this process. Identification of these proteins is the main focus of our work in this area.
Identifying gender-specific factors that control skeletal muscle glucose uptake for the treatment of type 2 diabetes following menopause.
Gender profoundly influences body composition and systemic glucose homeostasis. Intriguingly, despite having lower skeletal muscle mass, pre-menopausal women exhibit better whole body insulin sensitivity and higher rates of insulin-stimulated muscle glucose uptake compared to men. After menopause these beneficial effects are no longer present, suggesting that ovarian hormones play a critical role in this process. Unfortunately, the molecular and cellular factors linking ovarian hormone function to skeletal muscle glucose metabolism are currently not well understood. A critical barrier in preventing type 2 diabetes following menopause is the identification of the intracellular proteins that enhance insulin-stimulated muscle glucose uptake in pre-menopausal females. Identification of these proteins is the main focus of our work in this area.