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December 19, 2013DiabetesOpen Access

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

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Key result

Elevated mouse hepatic betatrophin expression induced by S961 treatment did not increase human beta-cell replication in transplanted human islets, which remained completely unresponsive.

Why the study?

Does administration of insulin receptor antagonist S961 (to increase betatrophin) stimulate replication of transplanted human β-cells?

Population

Mice with transplanted human β-cells under the kidney capsule and endogenous mouse β-cells in the pancreas

Design

Preclinical

Authors

YJYang JiaoJLJohn Le LayMYMing Yu

Discussion

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Overview

Casts doubt on betatrophin's therapeutic potential for human diabetes; leaves open species-specific β-cell regeneration strategies.

Structured PICO

Does administration of insulin receptor antagonist S961 (to increase betatrophin) stimulate replication of transplanted human β-cells?

P
Population
Human islets from 5 nondiabetic deceased organ donors (aged 4 to 53 years) transplanted into immunodeficient mice to assess beta-cell replication in response to betatrophin.
I
Intervention
Administration of insulin receptor antagonist S961 (to increase betatrophin gene expression)
O
Outcome
β-cell DNA replicationsurrogate

Main Result

Absolute Event Rate: 0.5% vs 0.5%

Betatrophin induction via S961 stimulates mouse but not human β-cell replication, casting doubt on its therapeutic potential for human diabetes.

Limitations

  • Human beta-cells were analyzed after transplantation under the kidney capsule, not in their normal location in the pancreas.
  • It is unknown whether mouse betatrophin can act on the human receptor.
  • Small number of human islet donors.

Cite This Study

Jiao et al. (2013) studied Diabetes (Beta-cell replication) (n=5). S961 (insulin receptor antagonist) vs. Vehicle (H2O) was evaluated on Human beta-cell replication rate (percentage of BrdU+/insulin+ cells). Elevated mouse hepatic betatrophin expression induced by S961 treatment did not increase human beta-cell replication in transplanted human islets, which remained completely unresponsive.

synapsesocial.com/papers/6a98705ba184c7fb06ada29ehttps://doi.org/10.2337/db13-1435
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