Table 1.

Factor	Role during Development	Role Postnatally
Transcription Factors
Pdx1	Growth and branching of pancreatic epithelium,6 required for endocrine cell differentiation,20 contributes to β cell proliferation21	Required to maintain β cell mass and β cell function27,69
Ptf1a	Evagination of pancreatic buds7	Acinar cell gene expression70
Ngn3	Initiation of endocrine cell differentiation8	Deletion of NGN3 in mature β cells impairs β cell function71
Sox9	Regulates the number of Ngn3 positive cells10	Haploinsufficiency results in glucose intolerance72
Hnf6	Required for Ngn3 expression9	Expressed in acinar cells and ducts73
MafA	Critical to Pdx1 expression only in the absence of MafB63	Important for expression of genes involved in β cell function24
MafB	Critical to the development of mature β cells,22 critical for Pdx1 expression63	Expressed in α cells74
FoxM1	No effect on β cell proliferation or β cell mass when inactivated38	Required for postnatal β cell proliferation36-38 regulates p27 expression38
FoxO1	Regulates Pdx1 transcription50	Negatively regulates β cell proliferation75
NFAT	Unknown	Inactivating studies show decreased β cell replication52
Growth Factors
CTGF	Required for β cell proliferation. Can induce α and β cell replication3,4	No effect on β cell proliferation when overexpressed (this study)
PDGF	Unknown	Regulates Ezh2 expression33
Placental Lactogen	Unknown	Stimulates β cell proliferation44,56
HGF	Unknown	Stimulates β cell proliferation by activating PI3 kinase76
Cell Cycle Activators
Cyclin D2	No effect on β cell mass when inactivated28	Contributes to β cell replication28
Cdk4	No effect on neogenesis29 but overexpression increases β cell proliferation77	Null mutants have decreased β cell proliferation at P1029
Cell Cycle Inhibitors
P27Kip1	Negatively regulates β cell proliferation; proliferation increased when inactivated18	No effect on β cell proliferation when inactivated in young adults; inactivation in older adults improves β cell proliferation18
P16Ink4a	Unknown	Inhibits β cell proliferation with knockouts having increased β cell proliferation30
Cell Cycle Inhibitor Regulators
Bmi1	Unknown	Regulates p16Ink4a 31
Ezh2	Unknown	Regulates p16Ink4a 32
Regulators of the PI3K/Akt Pathway
mTORC2 (Rictor)	Regulates p27 and FoxO149	Critical for β cell replication49
PDK1	Essential for β cell expansion78	Unknown
Other
Glucose	Ovine fetuses exposed to high glucose in utero showed increased β cell mass with no change in β cell proliferation79	Stimulates β cell proliferation45,46
PERK	Contributes to β cell proliferation16	Not required for β cell proliferation post-weaning16