Table 1.

Endothelial cells-derived factors involved in pancreas development

EC-factor	Mediatory pathway		Stage	Role(s)	LOF	References
EGFL7	EGFR, AKT(PKB)		E9.0_E11.5	• Increase PP proliferation • Decline differentiation to endocrine cells	• ND	[97, 203]
S1P	SPHK, S1P		E10.5	• Proliferation of PDX1+ PP	• Declined size of pancreatic buds • Hyper-vascularization	[204, 205]
CTGF		TGFβ, BMPs, Wnts	E12.5	• β-cell proliferation and islet morphogenesis	• Declined β-cell proliferation and islet vascularity	[206, 207]
TSP1 (THBS)		TGFβ-1	E12.5	• Antiangiogenic • Maintain postnatal β-cell function	• Hyperplasia in islets	[29, 208]
HGF		PI3K	E15	• Increase β-cell proliferation and islet mass	• Reduced islet size and insulin secretion • Glucose intolerance	[209–211]
BMP 2/4		TGFβ-1	ND	• Stimulate vasculogenesis and angiogenesis • Endothelial progenitor cell differentiation • Mediate GSIS	• ND	[78, 212]
ENDOGLIN		TGFβ	ND	• Islet vascular development	• Decreased insulin secretion	[213]
ENDOTHELINs		MAPK, PI3K	ND	• Stimulate β-cell insulin secretion • Effects on native islet blood vessels	• Vascular dysfunction	[214, 215]
ECM components*		Focal adhesion kinase	ND	• Increase Insulin gene expression • β-cell differentiation, maturation and survival	• ND	[29, 216]

LOF results of loss of function, ND no data provided, EC-factor endothelial cell-factors, EGFL7 epidermal growth factor‐like domain 7, S1P sphingosine-1-phosphate, CTGF connective tissue growth factor, TSP-1 Thrombospondin-1, HGF hepatocyte growth factor, BMP bone morphogenetic protein; VEGF vascular endothelial cell growth factor

^*Laminin/Collagen IV/Fibronectin