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Table 3 Small molecules and peptides used for beta cell differentiation from MSC. Physiological or biochemical actions and substitutes for the small molecules/peptides used to generate beta cells from different tissue-derived MSC

From: An overview on small molecule-induced differentiation of mesenchymal stem cells into beta cells for diabetic therapy

Small molecule or peptide—name

Structure

Mode of action and effect

Possible substitute

Ref

Nicotinamide

PARP inhibition, drives beta cell outgrowth

Not known

[131]

IDE-1 (inducer of definitive endoderm 1)

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Favors nodal signaling, induces Sox-17-reporter

IDE-2

[86, 116, 132]

l-Taurine (2-aminoethanesulfonic acid)

Cryoprotective agent binding with glycine receptors, involved in calcium signaling

Not known

[133]

Vitamin C

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Reducing p53 levels and lightening senescence, thereby inducing complete reprogramming

Not known

[134]

ILV (indolactam V)

Protein kinase C activation, can induce pancreatic progenitor differentiation

PbdU

[135, 136]

RA (retinoic acid)

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Receptor for retinoic acid receptors; promotes differentiation into neurons, glia cells, adipocytes

Not known

[136, 137]

SB203580

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MAP kinase (MAPKAP kinase-2 and P38 MAPK) inhibitor, heat shock protein inhibition

PD98059,

U0216

[138]

Trichostatin

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Class 1 and II histone deacetylase inhibitor, removes acetyl groups from the histone tails.

Not known

[139]

Sodium butyrate

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Class I inhibitor of histone deacetylases

Not known

[140]

Lithium chloride

Promotes Wnt signaling, blocks glycogen synthase kinase 3-β pathway

SB216763, CHIR99021

[141]

PD0325901

MEK/ERK kinase pathway inhibitor

Not known

[142]

LDN 193189

Inhibitor of ALK 1,2,3,6 pathways

Not known

[143]

DAPT

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Gamma secretase inhibition

Compound -E

[121]

Pentagastrin

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CCKB agonist, expands beta cell mass.

Not known

[144]

GLP-1

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Augments maturation, belongs to the group of hormones that reduce blood glucose by binding with GLP receptors

Exendin, Exenatide, semaglutide

[145, 146]

Exendin-4

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GLP receptors agonist

GLP-1

[147]