Elevated Mouse Hepatic Betatrophin Expression Does Not Increase Human β-Cell Replication in the Transplant Setting

  1. Klaus H. Kaestner1
  1. 1Department of Genetics and Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
  2. 2Department of Surgery and Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
  1. Corresponding author: Klaus H. Kaestner, kaestner{at}mail.med.upenn.edu.

Abstract

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 β-cells, has raised high hopes for the rapid development of a novel therapeutic approach for the treatment of diabetes. At present, however, the effects of betatrophin on human β-cells are not known. Here we use administration of the insulin receptor antagonist S961, shown to increase betatrophin gene expression and stimulate β-cell replication in mice, to test its effect on human β-cells. Although mouse β-cells, in their normal location in the pancreas or when transplanted under the kidney capsule, respond with a dramatic increase in β-cell DNA replication, human β-cells are completely unresponsive. These results put into question whether betatrophin can be developed as a therapeutic approach for treating human diabetes.

  • Received September 18, 2013.
  • Accepted December 6, 2013.

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.

No Related Web Pages
| Table of Contents

This Article

  1. Diabetes vol. 63 no. 4 1283-1288
  1. All Versions of this Article:
    1. db13-1435v1
    2. 63/4/1283 most recent