Normally, the number of beta cells a person has is not static, but change to adapt to a person’s changing metabolic demands such as during growth, weight gain or loss, or during pregnancy. JDRF’s Regeneration Program is focused on defining the mechanisms that regulate these normal changes in beta cell numbers and discovering drugs that can be used therapeutically to increase beta cell numbers in individuals with T1D. Recently, Dr. Rohit Kulkarni’s team at the Joslin Center and Dr. Doug Melton’s team at Harvard have independently reported the identification of two different factors capable of stimulating beta cell number expansion in mice. In his report, Dr. Kulkarni provides evidence that a massive expansion of beta cell numbers is regulated by a factor coming from the liver and acting directly on the beta cells to induce their growth and replication. The factor specifically and selectively induces beta cell expansion and acts on human beta cells as well as mouse beta cells. Dr. Melton and his team identified a novel hormone they called betatrophin, that appears to regulate beta cell expansion in an indirect manner in a mouse model of insulin resistance. When betatrophin is expressed in normal mice, it is capable of inducing expansion of beta cell mass without insulin resistance.
Ramifications for Individuals with T1D:
These early-stage, exploratory investigations have identified additional novel factors that regulate expansion of beta cell numbers to allow the body to respond to normal changing metabolic needs. Although much more work is required to demonstrate if these discoveries can be translated into beta cell regeneration therapies for individuals with T1D, if successful, these findings could lead to the development of novel drugs that safely and selectively stimulate expansion of beta cells in people with T1D to restore their normal insulin production and reduce or eliminate the need for external insulin injections.
The work in Dr. Kulkarni’s group was funded through the JDRF-Sanofi partnership. JDRF did not support the work in Dr. Melton’s group.
Investigators and Institutions:
These investigations were led by Dr. Rohit Kulkarni at the Joslin Diabetes Center and Dr. Douglas Melton at the Harvard Stem Cell Institute.
El Ouaamari A, Kawamori D, and others. Liver-derived systemic factors drive β cell hyperplasia in insulin-resistant states. Cell Rep. 2013 Feb 21;3(2):401-10.
Yi P, Park JS, Melton DA. Betatrophin: A Hormone that Controls Pancreatic Beta Cell Proliferation. Cell. 2013 May 9;153(4):747-58.