The recent discovery of betatrophin, a protein secreted by the liver and white adipose tissue in conditions of insulin resistance and shown to dramatically stimulate replication of mouse insulin-producing beta-cells, has raised high hopes for the rapid development of a novel therapeutic approach for the treatment of diabetes. However, at present the effects of betatrophin on human beta-cells are not known. Here we employ administration of the insulin receptor antagonist S961, shown to increase betatrophin gene expression and stimulate beta-cell replication in mice, to test its effect on human beta-cells. While mouse beta-cells, both in their normal location in the pancreas or when transplanted under the kidney capsule, respond with a dramatic increase in beta-cell DNA replication, human beta-cells are completely unresponsive. These results put into question whether betatrophin can be developed as a therapeutic for human diabetes.
- Received September 18, 2013.
- Accepted December 5, 2013.
- © 2013 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.