Pancreatic β cell regeneration induced by clinical and preclinical agents

Abstract

Diabetes, one of the most common chronic diseases in the modern world, has pancreatic β cell deficiency as a major part of its pathophysiological mechanism. Pancreatic regeneration is a potential therapeutic strategy for the recovery of β cell loss. However, endocrine islets have limited regenerative capacity, especially in adult humans. Almost all hypoglycemic drugs can protect β cells by inhibiting β cell apoptosis and dedifferentiation via correction of hyperglycemia and amelioration of the consequent inflammation and oxidative stress. Several agents, including glucagon-like peptide-1 and γ-aminobutyric acid, have been shown to promote β cell proliferation, which is considered the main source of the regenerated β cells in adult rodents, but with less clarity in humans. Pancreatic progenitor cells might exist and be activated under particular circumstances. Artemisinins and γ-aminobutyric acid can induce α-to-β cell conversion, although some disputes exist. Intestinal endocrine progenitors can transdeterminate into insulin-producing cells in the gut after FoxO1 deletion, and pharmacological research into FoxO1 inhibition is ongoing. Other cells, including pancreatic acinar cells, can transdifferentiate into β cells, and clinical and preclinical strategies are currently underway. In this review, we summarize the clinical and preclinical agents used in different approaches for β cell regeneration and make some suggestions regarding future perspectives for clinical application.

Keywords: β cell regeneration; β cell dedifferentiation; Cell proliferation; Pancreatic progenitors; α-to-β cell transdifferentiation; Enteroendocrine progenitor cells

Core Tip: Pancreatic regeneration is a potential therapeutic strategy for β cell recovery in diabetes. Previous studies have focused on the various cell types and different strategies for islet regeneration. However, how far this is from clinical application has not been fully elucidated. In this review, we focus on the clinical and preclinical agents used in different approaches. The clinical potential and disadvantages of the various approaches are discussed, and some suggestions are made for future perspectives.