Researchers from the La Jolla Institute and University of Virginia find protein key to insulin secretion
If you think of diabetes onset like an elaborate molecular drama, then a research team led by a La Jolla Institute scientist has unmasked a previously unknown cellular player, which is critical to proper insulin secretion. "Defective insulin secretion is a hallmark of both type 1 and type 2 diabetes," said Catherine Hedrick, Ph.D., a scientist at the La Jolla Institute for Allergy & Immunology, who led the team, which included researchers from the University of Virginia.
Working in mouse models, the team discovered that the ABCG1 protein is essential for the beta cells of the pancreas to produce sufficient amounts of insulin. Insulin is needed by the body to convert glucose from food into energy. Problems with insulin production underlie both type 1 and type 2 diabetes. "Based on our studies in mice, we think that some diabetes patients may have reduced expression of ABCG1 which impairs their insulin secretion," said Dr. Hedrick, who has previously published findings showing that type 2 diabetics have lower levels of ABCG1 than non-diabetics.
The research team also showed that proper expression of the ABCG1 protein in beta cells could be restored in the mice by treatment with some existing antidiabetic drugs. "Our study suggests that certain existing antidiabetic drugs may also provide therapeutic benefit related to restoring normal levels of ABCG1 protein in beta cells and improving insulin secretion in people with type 2 diabetes," said Dr. Hedrick. "Our research points to the need to investigate this possibility further as well as to explore the potential development of new therapies that boost ABCG1 protein levels and insulin secretion," she said.
The finding was published online today in the Journal of Clinical Investigation in a paper titled "An intracellular role for ABCG1-mediated cholesterol transport in the regulated secretory pathway of mouse pancreatic beta cells." Jeff Sturek, Ph.D., from the University of Virginia, was lead author on the paper and Dr. Hedrick, who was a faculty member at the University of Virginia before joining the La Jolla Institute in late 2009, was senior author.
Ann Marie Schmidt, Ph.D., the Gerald & Janet Carrus Professor of Surgical Science at Columbia University, who specializes in research on the mechanisms of diabetic complications, called the finding a "very novel and extremely important" discovery illuminating the ABCG1 protein's role in optimizing insulin secretion. "This mechanism may be very helpful for people with type 2 diabetes, but also type 1 because it may extend the period of time before all insulin-producing potential is gone," she said. "While delaying disease onset is important in both types of diabetes, it is particularly critical for type 1 diabetics who tend to manifest diabetes as children and who can suffer more severe disease consequences because of the lifelong nature of their illness and their eventual complete loss of the ability to produce insulin."
Matthias von Herrath, M.D., director of the La Jolla Institute's Type 1 Diabetes Research Center, agreed and praised the ABCG1 finding as an important step in understanding the cellular mechanisms of insulin secretion. "Dr. Hedrick's discovery offers important insights on possible ways to increase insulin production, which is key to controlling both types of diabetes," said Dr. von Herrath, who is among the world's leading type 1 diabetes researchers. "We are pleased that she recently joined our Institute and will be contributing to our Center's efforts to combat this terrible disease."