Diabetes is a disorder in which the cells of the body are not able to properly use the sugar glucose as a source of energy. This results in high levels of glucose circulating in the blood. Prolonged high levels of glucose are toxic, resulting in the many problems that patients with diabetes can develop over time, including kidney disease, blindness, and heart disease. A major part of the glucose regulatory system in the body is the beta-cell, which is located in the pancreas and produces a protein called insulin that functions as a key to unlock the insulin receptor, which functions to regulate other molecules that serve as a door on many cells in the body to allow glucose to enter.
Regardless of the type of diabetes, it is clear that dysfunction and eventual loss of the beta-cells plays a central role in the development of diabetes. In type I diabetes, also known as juvenile diabetes, the beta-cell are destroyed by the body's immune system, resulting in a almost complete lack of beta-cells and consequent insulin deficiency. In type II diabetes, which is strongly associated with obesity, the situation is more complex, with a combination of two major processes- resistance to the action of insulin combined with gradual dysfunction and loss of beta-cells- combining to produce a diabetic state. Thus, in both major forms of diabetes, beta-cell dysfunction and loss plays a central role and much effort is consequently being devoted to increasing the number of beta-cells, including from adult stem/progenitor cells, as proposed in this grant.
Recently, it has been demonstrated that stem/progenitor cells that can form new beta-cells are present in the adult human pancreas. To advance that finding into a therapy for diabetes requires a greater understanding of the nature of those cells and the process by which they become beta-cells. The experiments proposed in this grant are directed at just those issues. We propose to study the mechanism by which adult stem/progenitor cells become beta-cells and also to study possible markers expressed by those cells, which would facilitate their identification and manipulation.
Diabetes is epidemic in our society, including California, due in large part to the increase in obesity. It is estimated that more than six percent of all Californians are afflicted with diabetes. For minority populations, the number is up to ten percent, reflecting the higher levels of obesity in those populations, as well as genetic predispositions that are just beginning to be understood. Achieving the goal of this project, which is to develop a new treatment for diabetes based on inducing the formation of new beta-cells from stem cells, would have an enormous impact on the quality of life of those citizens.