Transdifferentiation of pancreatic α-cells into insulin-secreting cells: From experimental models to underlying mechanisms

Table 1 List of some experimental models of α-cell transdifferentiation

Experimental model	Phenotype	Intermediate cells	α-cell proliferation	Ref.
Pax4 overexpression	Converts progenitor cells into α and subsequently β cells	Very few	-	[24]
Arx inactivation	α- to β-like conversion	+	-	[25]
Arx inactivation; Pdx1;Arx double mutant	α- to β-like conversion	+	-	[26]
Pdx1 overexpression	α- to normal β cell conversion	Numerous mantle-located Gcg + Ins + cells were detected in P1-P12	-	[28]
PDL + alloxan	A large number of new β cells arising from adult α cells within 14 d	58% of Ins+ cells coexpressed glucagon	-	[30]
Extreme β-cell loss	α- to β-cell transdifferentiation	+	-	[29]
Treatment with histone methyltransferase inhibitor	α- to β-cell conversion	Colocalization of both glucagon and insulin in human and mouse islets	-	[36]
Ablation of glucagon gene	Normoglycemia and hyperplasia of pancreatic α cells	+	+	[31]
Ablation of glucagon receptor (Gcgr-/-)	Lower blood glucose, hyperglucagonemia, and pancreatic α-cell hyperplasia	Few scattered Gcg + Ins + cells or not mentioned	+	[27,32-34]
Impaired glucagon synthesis (SPC2-/-)	Normoglycemia, hyperplasia of pancreatic α and δ cells	Not mentioned	+	[37]
Disturbed glucagon pathway [Liver-specific G(s)alpha deficiency]	Hypoglycaemia, hypoinsulinemia, pancreatic α-cell hyperplasia		+	[38]
Men1 inactivation	α-cell transdifferentiation, α-cell hyperplasia and development of glucagonoma and insulinoma	+	+	[39]