Underlying Genetic Basis Of Human Alpha To Beta Cell Conversion Uncovered

One potential way to replenish lost beta cells in a person with T1D is by triggering other cells in the pancreas to function like insulin-producing beta cells. Previous JDRF-supported research has shown that pancreatic glucagon-producing alpha cells and insulin-producing beta cells are more adaptable to changing their biological function than previously thought and that under certain conditions alpha cells can spontaneously change into beta cells. However, the basis for this adaptability was not well understood. Dr. Klaus Kaestner and his team at the University of Pennsylvania used special techniques to look at which genes were “switched on” or “switched off” in alpha and beta cells to learn more about how this conversion process works.  Focusing on genes that are normally only expressed in either beta cells or alpha cells, the team found that beta cells tended to have the beta cell-specific genes clearly “switched on” and the alpha cell-specific genes clearly “switched off”. In contrast, when the team examined the alpha cells, they found that while alpha cell-specific genes were clearly “switched on” as expected, the beta cell-specific genes appeared to be “switched on” and “switched off” simultaneously.   Although this does not result in expression of the beta cell genes in alpha cells, this unique pattern helps to explain why alpha cells can be readily converted into beta cells and suggests ways that the process could be manipulated as another approach to regenerating lost beta cells in people with T1D.

Ramifications for Individuals with T1D:

This early stage, exploratory research further supports the feasibility of stimulating alpha to beta cell conversion as a potential therapy for people with T1D and begins to identify potential mechanisms to promote this conversion. More work will be required to identify discrete drug targets and assess suitability for translation into drug discovery programs.

JDRF Involvement:

None

Investigators and Institutions:

This work was led by Dr. Klaus Kaestner at the University of Pennsylvania.

Reference:

Bramswig NC, Everett LJ, and others. Epigenomic plasticity enables human pancreatic alpha to beta cell reprogramming. J Clin Invest. 2013 Mar 1;123(3):1275-84.