In people who put on a lot of weight, or whose bodies start developing the inability to use insulin effectively that leads toward type 2 diabetes, the pancreas typically ramps up its supply of insulin-generating "beta" cells, at least partly by replication of the existing cells.
Researchers at Joslin Diabetes Center and their colleagues now have identified a cell-cycle protein that is essential for beta-cell replication to respond successfully to insulin resistance. The finding may point toward eventual therapies for preventing or treating type 2 diabetes.
In a paper published in Diabetes on January 26, biologists in the labs of Joslin Principal Investigator Rohit N. Kulkarni, M.D., Ph.D., and Anil Bhushan, Ph.D., at the University of California at Los Angeles used a genetic approach to show that a protein called cyclin D2 is needed for this beta-cell response in mice.
Cyclin D2 is a member of a small family of proteins that aid in the cell cycle, by which cells divide into two. Earlier studies had demonstrated that cyclin D2 is particularly important to the replication of beta cells but had not directly addressed its role in insulin resistance.
The researchers began with two existing mouse models that develop insulin resistance—one mild case and one more severe case, reflecting the spectrum observed in humans with type 2 diabetes. Each of the models ends up generating many more beta cells. When these mice were crossed with mice lacking cyclin D2, all their progeny developed diabetes because they produced dramatically fewer beta cells.
This work provides direct evidence in mice that cyclin D2 is needed for a successful response to a broad spectrum of insulin resistance, and points toward potential therapies that can be harnessed for preventing and curing type 2 diabetes.