Drug Shown to Trigger Beta Cell Regeneration

A number of peptides, nutrients and metabolites have been implicated as regulators of the number of beta cell and regeneration. One class of molecule, lisophospholipids, have been shown to be increasing during times of expanding beta cell numbers such as pregnancy and obesity, but their role in regulating these events is not well understood. Dr. Mas team tested a number of lisophospholipids and related molecules to determine if any were capable of stimulating beta cell proliferation in the lab and in mouse models of diabetes. They found that one such compound called fingolimod (or FTY720), can induce beta cell proliferation and increase beta cell numbers and restore glucose control in a mouse model of T2D. Fingolimod is currently in clinical testing as an immune therapy for the treatment of certain forms of multiple sclerosis, but is associated with side effects that would make it unsuitable for treatment of T1D. Further efforts will be required to identify new compounds like fingolimod that work more specifically in beta cells and avoid unwanted side effects.

Reference:

Zhao Z, Choi J, Zhao C Ma ZA. FTY720 normalizes hyperglycemia by stimulating beta-cell in-vivo regeneration in db/db mice through regulation of cyclin D3 and p57­KIP2. J. Biol. Chem. February 2012;287(8):5562-73

Ramifications for Individuals with Type 1 Diabetes:

This early work suggests that activation of the lisophospholipid-related pathway could be used to induce beta cell regeneration in T1D. More work is required to identify safe and selective therapeutic strategies to activate this pathway only in beta cells, avoiding the side effects associated with similar drugs that are already in clinical use.

JDRF Involvement:

None.