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April 27, 2015DiabetologiaOpen Access

Angiopoietin-like protein 8 (ANGPTL8)/betatrophin overexpression does not increase beta cell proliferation in mice

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Key result

ANGPTL8 overexpression does not stimulate beta cell replication or expand beta cell mass in young or old mice, contradicting previous reports of its role as a betatrophin.

Population

Multiple cohorts of male mice including B6.129 and ICR strains.

Comparison

Hydrodynamic tail vein injection of Angptl8 DNA… vs Hydrodynamic tail vein injection of green…

Design

Preclinical

Follow-up

8 days

Authors

ACAaron R. CoxThe University of Texas Health Science Center at HoustonCLCarol J. LamChildren's Hospital of PhiladelphiaCBClaire W. BonnymanTexas Scottish Rite Hospital for Children

Discussion

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Member takes

Overview

Questions ANGPTL8 targeting for beta-cell regeneration; challenges prior reports and leaves therapeutic potential open.

Structured PICO

P
Population
59 male mice of various strains (B6.129 and ICR) and ages (7 weeks to 16 months) were studied to evaluate the effect of ANGPTL8 overexpression on beta cell proliferation.
I
Intervention
Hydrodynamic tail vein injection of Angptl8 (Gm6484) DNA (100 mg) with sleeping beauty transposase plasmid (4 mg).
C
Comparator
Hydrodynamic tail vein injection of green fluorescent protein (GFP) DNA.
O
Outcome
Beta cell proliferation (quantified by Ki67 and EdU incorporation) and beta cell mass at 8 days post-injection.surrogate

ANGPTL8 (betatrophin) overexpression does not stimulate beta cell replication or expand beta cell mass in mice, challenging previous hypotheses regarding its therapeutic potential for diabetes.

Limitations

  • Animal model (mice) may not fully translate to human beta cell biology
  • Potential technical differences from previous studies despite attempts to replicate them

Cite This Study

Cox et al. (2015) studied Beta cell proliferation (n=59). ANGPTL8 (betatrophin) overexpression vs. Green fluorescent protein (GFP) DNA injection was evaluated on Beta cell proliferation (Ki67+ or EdU+ beta cell ratios) and beta cell mass. ANGPTL8 overexpression does not stimulate beta cell replication or expand beta cell mass in young or old mice, contradicting previous reports of its role as a betatrophin.

synapsesocial.com/papers/6a98705ba184c7fb06ada295https://doi.org/10.1007/s00125-015-3590-z
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Elevated Mouse Hepatic Betatrophin Expression Does Not Increase Human β-Cell Replication in the Transplant Setting2013 · 118 citations
  2. 2Betatrophin Versus Bitter-Trophin and the Elephant in the Room: Time for a New Normal in β-Cell Regeneration Research2014 · 35 citations
  3. 3Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism2012 · 301 citations
  4. 4Evidence for a circulating islet cell growth factor in insulin-resistant states2001 · 156 citations
  5. 5Adaptive β-Cell Proliferation Is Severely Restricted With Advanced Age2009 · 324 citations