Focusing on the properties that endow beta cells with the unique ability to manufacture insulin, Institute researchers hope to develop a new treatment for Type 1 diabetes, as well as a new method for its early diagnosis and prevention.
Among the key molecules involved in insulin production are transcription factors - proteins that determine which genes are switched on in a cell. A group led by Prof. Michael Walker of the Department of Biological Chemistry has shown that switching on the insulin gene in beta cells is a complex process involving at least four transcription factors.
Walker’s group recently showed that these four proteins cooperate in switching on insulin production, thus explaining a large part of the previously mysterious ability of beta cells to produce this hormone. In collaboration with the Sheba Medical Center of Tel Hashomer Hospital, the researchers are currently implanting transcription factors into liver cells in the aim of activating the otherwise silent insulin gene. The approach of engineering cells taken from a patient to produce insulin may provide the basis for a cure for Type 1 diabetes.
In a related project, Walker and colleagues have identified several previously unknown proteins produced preferentially in beta cells. Since the autoimmune attack in Type 1 diabetes is probably directed against a number of such proteins, the newly identified molecules may help reveal the precise protein fragments that serve as targets of attack (adding to the protein already identified by the Institute’s Prof. Cohen). Working in collaboration with the Felsenstein Medical Research Center in Petah Tikva, Walker is seeking to determine whether antibodies from diabetic patients recognize these proteins. If so, this research may yield useful early markers for high-risk individuals.
One of the newly identified proteins is a membrane-bound receptor designated GPR40. Walker’s team is using genetically modified mice to understand the role of GPR40 in the beta cell - a study that may lead to a better understanding of how beta cells become defective in Type 2 diabetics.