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Table 1 Conditions that promote β-cell regeneration

From: In vivo generation and regeneration of β cells in zebrafish

 

Inducer

Effects

Developmental stage

Cell source

Related mechanism

Modifer Screen

Gene/target identified

Related pathway

Reference

Manipulation of Insulin signaling

Transgenic expression of a dominant-negative IGF1R

Insulin resistance

Embrynonic, Larval and adult

Progenitors and β cells

Proliferation

None

igf1r

Insulin signalling

(Maddison et al., 2015)

Knockout of insra/insrb

Insulin resistance

Embryonic and larval

Unknown

N.A.

None

insra/insrb

Insulin signalling

(Yang et al., 2017)

Transgenic expression of a dominant-negative IRS2

Insulin resistance

Embryonic

Progenitors

Neogenesis

None

irs2

Insulin signalling

(Ye et al., 2016)

Nutrient

Increased insulin demand

larval

Progenitors

Neogenesis

Candidate drugs

fgf1/rapamycin

FGF, mTORC1

(Maddison & Chen, 2012; Li et al., 2014)

Nutrient

Increased insulin demand

Larval

Progenitors and β cells

Neogenesis

Candidate drugs

g secretase inhibitor and rapamycin

Notch, mTORC1

(Ninov et al., 2013)

β-cell ablation

Decreased insulin supply

Larval

Progenitors and β cells

Neogenesis

Chemical library

Adenosine Receptor A2aa (agonist)

Adenosinergic

(Andersson et al., 2012; Schulz et al., 2016)

β-cell ablation

Decreased insulin supply

Larval

β cells

Proliferation

Chemical library

TBK1/IKKε (inhibitor)

PKA, mTORC1

(Xu et al., 2018)

β-cell ablation

Decreased insulin supply

Larval

Progenitors

Neogenesis

Mutation

Sox9b

Retinoic acid signaling; Notch signaling

(Manfroid et al., 2012; Huang et al., 2016)

β-cell ablation

Decreased insulin supply

Larval

Progenitors

Neogenesis

Mutation

Dnmt1

N.A.

(Anderson et al., 2009)

β-cell ablation

Decreased insulin supply

Larval

Progenitors

Neogenesis

Mutation

fhl1b

N.A.

(Xu et al., 2016)

β-cell ablation

Decreased insulin supply

Larval

α cells

Trandedifferentiation

Morpholino, antibody

gcg

non-gluconeogenic effects of glucagon

(Ye et al., 2015)

β-cell ablation

Decreased insulin supply

Larval

α cells

Trandedifferentiation

Mutation

Igfbp1

IGF1 signaling

(Lu et al., 2016)

Chemical genetics

Chemicals

Inhibition or activation of drug targets

Larval

Progenitors

Neogenesis

None

ALDH1A1 (inhibitor), IMPDH (inhibitor)

RA, Nucleotide synthesis

(Rovira et al., 2011; Shen et al., 2013)

Chemicals

Inhibition or activation of drug targets

Larval

Progenitors and β cells

Proliferation/ Neogenesis

None

NFkb activators, Serotonergic activators

NFkB, Serotonergic, glucorcorticoid analogs

(Wang et al., 2015; Janjuha et al., 2018)

Chemicals

Inhibition or activation of drug targets

Larval

β cells

Proliferation

None

RXR agonists, serotonin boosters, GR agonists

RA, Serotonergic, glucocorticoid

(Tsuji et al., 2014)

Notch inhibition

Precocious β-cell differentiation

Larval

Progenitors

Neogenesis

Chemical library

CDK5 (inhibitor)

N.A.

(Liu et al., 2018)

Other

Microbiota

Unknown

Larval

Progenitors

Proliferation

larvae stage

BefA

N.A.

(Hill et al., 2016)

CDK4

Cell division activation

Larval

β cells

Proliferation

larvae stage

Cyclin-Dependent Kinase 4

N.A.

(Li et al., 2013)

Genetic Lineage Tracing

Suppression of target gene

embryonic development

Acinar

Trandedifferentiation

None

Ptf1α

N.A.

(Hesselson et al., 2011; Dong et al., 2008)