Table 1.

Pathways Toward β-cell Regeneration

Pathway	Physiologic Conditions	Environmental Triggers	*Biologic Factors	*Small Molecules/Transcription Factors
β-Cell Expansion	Pregnancy12-14 Obesity15-20 Insulin Resistance21-22 Development28-30	β-Cell Ablation23-27 Partial Pancreatectomy41	Glucose47-48 GLP-1 Betatrophin54 Serotonin62 Lactogens14,58-62 Osteocalcin58-59	**cMyc, ChREBP, NKX6.1, Cdk6, FoxM135-39 Glucokinase activators, Sulfonylureas50 L-type calcium channel agonists, phorbol esters, Wnt agonists51 WS664 Adenosine agonists66 Adenosine Kinase Inhibitors (ADKI's)65-66
β-Cell Neogenesis	Development	Pancreatic Duct Ligation/Partial Pancreatectomy27,79-83,88-91	-	Pax487,91
β-Cell Trans-differentiation	-	β-Cell Ablation23,116	-	Pdx1101 NeuroD +/− Betacellulin102 Pdx1+NeuroD/Ngn3103 Pdx1+MafA+Ngn3/NeuroD105 **Combinatorial Culture Conditions107 BRD7389110 FoxO1118

^*Biologic factors and small molecules listed are limited to those discussed in the review

^**In-vitro