Project Details
Projekt
Role of a new vitamin K-dependent protein in beta cell function and diabetes
Applicant
Dr. Angela Pelligra
Subject Area
Endocrinology, Diabetology, Metabolism
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 585111238
Type 2 diabetes is one of the fastest-growing chronic diseases worldwide. It occurs when the body stops responding properly to insulin—a hormone that controls blood sugar—and when the insulin-producing cells in the pancreas, called beta cells, gradually lose their ability to work and eventually die. Because these cells cannot regenerate, protecting them is critical to prevent or slow the progression of type 2 diabetes. Current treatments cannot restore beta cell function or stop their decline. Vitamin K, best known for helping blood coagulation, may also play an important role in keeping beta cells healthy. Studies show that people with low vitamin K levels have a higher risk of developing type 2 diabetes, but we still do not fully understand why. Our lab discovered that vitamin K helps beta cells function through a process called gamma-carboxylation. This process modifies certain proteins inside beta cells allowing them to adjust insulin production based on sugar levels. When this process is disrupted, beta cells release too much insulin—even at low blood sugar levels—which can lead to insulin resistance. We also identified a new vitamin K-dependent protein called ERGP (Endoplasmic Reticulum Gla Protein). ERGP helps control calcium inside beta cells. Calcium is essential for insulin release, but too much calcium stresses the cells and disrupts their coordination. A lack of vitamin K may also interfere with communication between beta cells, which is vital for proper insulin secretion. To better understand these mechanisms, my research will focus on three goals: 1. Determine ERGP’s role in blood sugar control and insulin secretion: Using mice that lack ERGP specifically in beta cells, I will study how this protein affects blood sugar and beta cell health under normal and stressful conditions. 2. Uncover how ERGP regulates calcium inside beta cells: I will examine how ERGP interacts with other proteins to control calcium and what happens when this interaction is impaired. 3. Explore how these processes affect communication between beta cells in mice and humans: I will study how beta cells coordinate their activity under different conditions. By clarifying how vitamin K and ERGP protect beta cells, this research could open the door to new treatments that slow or prevent type 2 diabetes. Ultimately, these discoveries may lead to drugs that restore beta cell function and improve long-term blood sugar control. Such advances could significantly reduce the burden of diabetes on patients, improving quality of life and lowering the risk of complications.
DFG Programme
Fellowship
International Connection
Canada
