Pancreatic β Cell Regeneration as a Possible Therapy for Diabetes

Abstract

Diabetes is the result of having inadequate supply of functional insulin-producing β cells. Two possible approaches for replenishing the β cells are: (1) replacement by transplanting cadaveric islets or β cells derived from human embryonic stem cells/induced pluripotent stem cells and (2) induction of endogenous regeneration. This review focuses on endogenous regeneration, which can follow two pathways: enhanced replication of existing β cells and formation of new β cells from cells not expressing insulin, either by conversion from a differentiated cell type (transdifferentiation) or differentiation from progenitors (neogenesis). Exciting progress on both pathways suggest that regeneration may have therapeutic promise.

Pancreas regeneration

“…There is a long-standing hypothesis that pancreatic stem or progenitor cells might exist in the adult animal or even human pancreas 34 . This hypothesis was initially based on histological observations of single islet cells and small islets embedded in or closely associated with adult rodent and human pancreatic ducts, suggesting the emergence of new islet cells from ducts (referred to as neogenesis) 34 .…”

“…This hypothesis was initially based on histological observations of single islet cells and small islets embedded in or closely associated with adult rodent and human pancreatic ducts, suggesting the emergence of new islet cells from ducts (referred to as neogenesis) 34 . However, genetic lineage-tracing studies using exocrine drivers ( Muc1 -CreER), acinar-specific drivers ( Cela -CreER, Ptf1a -CreER), and duct-specific drivers ( Sox9 -CreER, Hnf1b -CreER) 35–39 consistently indicated rare or no contribution from the exocrine to the endocrine compartment during normal homeostasis or in various injury models.…”

Immunophenotypes of Ductal Epithelial Cells in Advanced Pancreatic Ductal Adenocarcinoma

“…In pathology, pancreatic β-cell loss (insulin insufficiency) is one of major causes of diabetes mellitus, especially in Type 1 [13]. To combat insulin deficit in diabetes by identifying potential origin of β cell neogenesis, ductal-derived insulin-producing cells are of great interest [14]. However, information about investigation regarding PDAC-originated islet cell neogenesis remains unknown.…”

Gimmicks of gamma‐aminobutyric acid (GABA) in pancreatic β‐cell regeneration through transdifferentiation of pancreatic α‐ to β‐cells

“…The most promising way for curing diabetes is islet transplantation, mostly focused on T1DM patients (Kuise and Noguchi, 2011), but donor shortage and life‐long need for immunosuppressive drugs make it less feasible for a routine clinical procedure (Benthuysen et al, 2016). Given these difficulties, over the last three decades, various methods have been attempted to regenerate/replace functional β cells in diabetic patients (Corritore et al, 2016; Aguayo‐Mazzucato and Bonner‐Weir, 2018; Zhou and Melton, 2018; Ghani et al, 2019).…”