The Medical College of Wisconsin (MCW) has received a six-year, $266,000 grant from the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases to study the science of diabetes at a cellular level.
Megan Determan, a third year graduate student in the department of cell biology, neurobiology, and anatomy, is the primary investigator of the grant. Determan is enrolled in MCW’s Medical Scientist Training Program, which combines curricula of medical school and graduate school.
According to the Centers for Disease Control, one in ten Americans has diabetes, and that number is expected to double or triple by 2050. Diabetes is the leading cause of kidney failure and blindness in older adults, and the disease doubles the risk of heart attack and stroke. The cellular mechanisms causing diabetes are not well understood.
In this project, Determan will study the most prevalent form of monogenic diabetes (diabetes caused by a mutation in one gene), which is called HNF1A-MODY. In that specific type of diabetes, only one copy of the HNF1A gene is functional.
Using stem cells induced from skin samples obtained from adults with the disease, and stem cells induced from healthy adults, the research team will create hepatocytes (liver cells) and identify changes in gene transcription in the mutant cells. Determan will also generate pancreatic beta cells, some from diabetic patients, and others from healthy patients, to evaluate glucose-response and insulin secretion.
The results should establish which molecular mechanisms are altered in the liver and pancreas cells in patients with monogenic diabetes caused by the HNF1A mutation and characterize the phenotype of these cells.
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