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March 13, 2014DiabetesOpen Access

Betatrophin Versus Bitter-Trophin and the Elephant in the Room: Time for a New Normal in β-Cell Regeneration Research

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Key result

Despite numerous agonists inducing robust β-cell replication in nonhuman species, very few induce human β-cells to replicate at therapeutically meaningful rates.

Population

Pancreatic β-cells in nonhuman species (mice, rats, pigs, zebra fish) and humans

Design

Editorial

Authors

ASAndrew F. StewartAllen Institute for Brain Science

Discussion

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Overview

β-cell regeneration therapies remain unavailable for clinical use; leaves open the need for human-specific mitogens and models.

Key Points

  • To examine the disconnect between successful β-cell replication achieved in animal models and the lack of therapeutic replication in human β-cells.
  • Narrative review and perspective synthesizing historical and contemporary research on pancreatic β-cell replication agonists.
  • Comparative analysis of proliferation responses across animal models, including mice, rats, pigs, and zebrafish, versus adult human β-cells.
  • Numerous agonists, including nutrients, growth factors, intracellular signaling molecules, and proteins, induce robust β-cell proliferation and expansion in rodent and nonhuman models.
  • A vast majority of validated animal agonists fail to induce human β-cells to replicate at therapeutically meaningful rates, presenting a substantial barrier to clinical translation.

Structured PICO

P
Population
Pancreatic β-cells in nonhuman species (mice, rats, pigs, zebra fish) and humans
E
Exposure
Agonists inducing β-cell replication (nutrients, growth factors, intracellular signaling molecules, small molecules, proteins)
O
Outcome
β-cell replication and expansion

Highlights the critical translational gap in β-cell regeneration research, where successful replication in animal models rarely translates to adult human β-cells.

Cite This Study

Andrew F. Stewart (2014) conducted an editorial in Type 1 and Type 2 Diabetes. β-cell replication agonists was evaluated on Human β-cell replication. Despite numerous agonists inducing robust β-cell replication in nonhuman species, very few induce human β-cells to replicate at therapeutically meaningful rates.

synapsesocial.com/papers/6a98705ba184c7fb06ada29chttps://doi.org/10.2337/db14-0009
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