Research Description
The hormone estrogen improves the function of the insulin-secreting beta cell and protects beta cells from cell death even in the face of metabolic stress. Estrogen levels in women fall with age, leaving beta cells at risk for damage and increasing diabetes prevalence in post-menopausal women. Systemic hormone replacement therapy can improve diabetes outcomes but has side effects, like strokes, heart attacks, and breast cancer. We propose restoring estrogen activity, specifically in beta cells, to enhance insulin secretion while avoiding the side effects of systemic hormone replacement therapy. We will develop a pre-clinical model of age-associated diabetes onset in females and deliver estrogen specifically to beta cells to test whether we can decrease diabetes incidence in an older population of females susceptible to diabetes.Research Profile
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?This project aims to address two aspects of diabetes in women. Women have increased rates of diabetes after menopause, associated with a decrease in estrogen, and having gestational diabetes also increases diabetes risk later in life. We will first investigate whether the increased diabetes incidence observed in women after gestational diabetes is caused by having gestational diabetes or whether underlying beta-cell defects cause gestational diabetes and re-emerge later in life. Second, we will attempt to improve insulin secretion and preserve beta cells in aged females by delivering estrogen directly to beta cells. We will use two mouse models: aged, obese female mice and aged female mice that experienced gestational diabetes earlier in life. This project will help us understand whether aggressive treatment of gestational diabetes could help prevent diabetes later in life. Further, estrogen delivery specifically to beta cells could improve insulin secretion and prevent or treat diabetes without causing side effects like breast cancer or cardiovascular events observed with whole-body estrogen delivery.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?This project could yield a new drug for treating diabetes. Even though we are beginning with females, this specific project might also directly result in treatment in men. Further, if successful, this project will demonstrate the feasibility of delivering drugs specifically to beta cells, and drugs other than estrogen could be used.
Why important for you, personally, to become involved in diabetes research? What role will this award play?Many of my family members have diabetes and I've seen the toll it has taken on their lives. Since over 10% of people in the United States have diabetes, I know that my experience is not unique. This award allows my colleagues and me to test a novel method of drug delivery to beta cells and has the potential for the development of a whole suite of beta-cell targeted drugs that, without such specificity, are dangerous or toxic to the whole body.
In what direction do you see the future of diabetes research going?In addition to tissue-specific delivery, I predict the development of drugs specific for the emerging subtypes of type 2 diabetes.