Partial Duct Ligation: β-Cell Proliferation and Beyond

Long-term evolution of acinar-to-ductal metaplasia and β-cell mass after radiofrequency-assisted transection of the pancreas in a controlled large animal model

“…This model has also demonstrated a complete acinar cell deletion in short and long-term evolution with no evidence of acinar compartment regeneration. These results are in contrast to other mouse models [6,7] and even pig models with simple ligation of the main pancreatic duct close to the duodenum -likely because of possible accessory drainages- [19,28,29] in which some regeneration of acinar tissue occurred. Although, the model results in the appearance of ADM in the short term RFAT group, as described after PDL [12,16,30], we have demonstrated the reduction of the ADM area in the long-term group compared to the short-term group (from 56% to 21% of the cross-sectional area), in spite of the growth of the animal.…”

“…Since complete duct occlusion should prevent duct cells regenerating into acinar cells after PDL [16] and some morphometric results could have been biased by including injured pancreas [7,11], the present study implemented six key differences from conventional PDL mouse models in order to ensure efficient and reliable pancreatic duct occlusion and accurate evaluation:…”

“…However, the validity of PDL as a model of endocrine regeneration has now been called into question [5][6][7]11,13,14]. Recent results from PDL in mouse models have shown that some acinar cells can escape death [7] and that acinar compartment can regenerate in a long-term evolution after PDL (over 6 months), probably by restoration of pancreatic drainage [6]. Ever since the first studies on PDL in mouse models it has been said that this technique is difficult because its unique anatomy hampers the results [15,16].…”

“…Pancreatic duct ligation (PDL) in mouse models has been extensively used as a model of chronic pancreatitis in order to study the evolution of ADM into PDAC [1,3,7], and also as a model of duct-to-islet differentiation [6,[8][9][10][11][12] to increase beta-cell mass. However, the validity of PDL as a model of endocrine regeneration has now been called into question [5][6][7]11,13,14].…”

Beta Cell Regeneration: A Novel Strategy for Treating Type 1 Diabetes

“…The first category includes factors deeply involved in the development and differentiation of pancreatic beta cells. These factors include cyclin D1/D2, cyclindependent kinase 4 (CDK4), glucagon-like peptide-1 (GLP-1), Neurogenin 3 (Ngn3), pancreatic duodenal homeobox-1 (Pdx1) etc [6][7][8][9]. However, the molecular pathways bridging these factors were not thoroughly understood.…”