Research Summary

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.

Lab Team

Carol Witczak, PhD

Associate Investigator, IBRI Diabetes Center

Postdoctoral Fellow 2008 Harvard University

PhD 2003 University of Missouri | BA 1998 Colgate University

READ CAROL'S BIO 

Parker Evans

Parker Evans

PhD Student, IBRI Diabetes Center

Parker Evans

Parker Evans

PhD Student, IBRI Diabetes Center

Parker Evans is a Bioenergetics and Exercise Science PhD student in Carol Witczak’s lab. He is working with Carol to complete his research for his PhD, which focuses on the subcellular localization of Glucose Transporter 6 (GLUT6) in skeletal muscle, as well as the role of GLUT6 in functional overload, a rodent model of resistance exercise.

Prior to joining the IBRI, Parker was a presenter at the FASEB Science Research Conference focused on The Regulation of Glucose Metabolism. His presentation centered around research about how female mice are protected against high fat diet-induced hyperinsulinemia and insulin resistance but not hyperglycemia or glucose intolerance compared to males.

Parker obtained his Bachelor of Science degree in Exercise Science from Brigham Young University in Provo, Utah, in 2017.

Carol Witczak

Carol Witczak

Associate Investigator, IBRI Diabetes Center

Carol Witczak

Carol Witczak

Associate Investigator, IBRI Diabetes Center

Carol Witczak joined the IBRI in December 2019 to establish a lab that will research the regulation of glucose transport in skeletal muscle. This research is vital to the Diabetes Center because while people with type 2 diabetes have decreased muscle glucose uptake in response to the hormone insulin, they have a normal ability to take up glucose in response to exercise. 

A specific focus of Carol’s research is resistance exercise training. She seeks to better understand the complex metabolic adaptations that occur in enlarging muscles, and how these adaptations could be exploited to develop new treatments for type 2 diabetes.

Prior to her arrival in Indiana she was an Associate Professor at East Carolina University in Greenville, North Carolina. At East Carolina University she focused on understanding the molecular and cellular factors that regulate muscle metabolism in both physiological and pathological conditions, including exercise, diabetes and cachexia.

Carol received her Bachelor of Arts degree in Molecular Biology from Colgate University in Hamilton, New York, in 1998. She obtained her PhD in Physiology from the University of Missouri in Columbia, Missouri, in 2003.