News & Research

    University of Pittsburgh, Pittsburgh, Pennsylvania

Activation of the early and late G1/S cell cycle molecules as a means of enhancing human beta cell regeneration

General Research Subject: Both Type 1 And Type 2 Diabetes

Focus: Islet Biology, Islet Biology\Beta Cell Growth and Differentiation

Type of Grant: Basic Science

Project Start Date: July 1, 2012

Project End Date: June 30, 2015

Research Description

Diabetes has reached epidemic proportions worldwide.  A major goal of diabetes research is to induce human beta cell replication and regeneration with enhanced beta cell function.  We have shown that overexpression in human beta cell of cell cycle molecules, such as cyclin D3 and cdk6, result, for the first time, in a significant replication, both in vitro and in vivo, with retained normalization of glycemic control in vivo.  But this induction of proliferation is still limited to only 10-15% of human beta-cells. Thus, we have chosen to determine the mechanisms through which human beta-cells proliferate, can be manipulated in order to further induce human beta-cell replication. The proposed studies will shed light on how best to induce therapeutic human beta cell replication and regeneration.

Research Profile

What area of diabetes research does your project cover?  What role will this particular project play in preventing, treating and/or curing diabetes?

Both Type 1 and Type 2 diabetes result from a complete or partial loss of beta cell (the insulin producing cells) number and function. Thus, from a therapeutic standpoint, activating the regeneration of human beta cells could prevent, or even reverse the onset of diabetes. Multiple approaches have been developed. They include: regeneration of endogenous beta cells, induction of human beta cells from human embryonic stem cell or pluripotent stem cells, using xeno-sources (pig or non-human primate islets) as a source of beta cells, as well as reprogramming of hepatocytes, exocrine pancreatic cells or other differentiated cell types, and, finally, expansion of cadaveric human beta cells. In any case, there is a clear need to expand human beta cells, regardless of their origin. Thus, we have chosen to determine the mechanisms through which human beta cells proliferate, and moreover how the cell cycle can be manipulated in order to induce human beta cell proliferation.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

It is now clear that beta cell replacement can reverse diabetes in humans.  One way to replace beta cells is to induce the regeneration of the endogenous beta cells or to expend cadaveric human beta cells for transplant. However, we know little as to how we can best induce human beta cell replication and regeneration. Therefore, information on human beta cell replication is critical to develop drug therapies for diabetes. Our study proposes to define new key molecules important for the regulation of beta cell replication.

Why is it important for you, personally, to become involved in diabetes research?  What role will this award play in your research efforts?

Diabetes has reached epidemic proportions worldwide. And the number of new patients diagnosed with diabetes increases everyday. We all know someone in our close family or friends with the disease. We are all concerned.  I hope that this award will permit to better understand the mechanisms through which we can best induce human beta cell regeneration.

In what direction do you see the future of diabetes research going?

We regard these as exciting and important experiments to further define molecular avenues to enhance human beta cell proliferation. We believe that data generated from these studies may lead to better knowledge of the regulation of human beta cell proliferation and how we can meaningfully therapeutically manipulate cell cycle molecules to induce human beta cell proliferation and design drugs that would achieve this purpose.