Elevated mouse hepatic betatrophin expression does not increase human beta-cell replication in the transplant setting

  1. Klaus H. Kaestner1,*
  1. 1 Department of Genetics and Institute for Diabetes, Obesity and Metabolism; University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.
  2. 2 Department of Surgery and Institute for Diabetes, Obesity and Metabolism; University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.
  1. *Correspondence to: Klaus H. Kaestner, E-mail: 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 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.

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  1. Diabetes
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