Reg2, also known as regenerating islet-derived protein 2 or Reg II (human ortholog Reg1B), is a gene with diverse functions. In mammals, it acts as a trophic factor stimulating β -cell replication in pancreatic islets, crucial for maintaining normal insulin production and glucose homeostasis [1,3,4,7]. It is also involved in the redox-related regulation of insulin secretion through its interaction with the transmembrane L-type voltage-dependent Ca2+ channel (CaV1.2) [2]. In the liver, it plays a role in protecting against Fas-induced oxidative stress and promoting liver regeneration [5]. In yeast (Saccharomyces cerevisiae), the REG2 gene encodes a type 1 protein phosphatase-binding protein that functions with Reg1p and the Snf1 protein kinase to regulate growth [6,8].

In Reg2 gene-deficient (Reg2-/-) mice, at a young age, there is no obvious change in normal islet morphology or glucose tolerance. However, 13-to 14-month-old Reg2-/-mice develop glucose intolerance, associated with decreased islet β-cell ratio and serum insulin level. After young mice are fed a high-fat diet, Reg2-/-mice show diminished islet mass expansion and serum insulin level, along with a decline in β-cell proliferation rate [3]. In the liver, Reg2-/-mice are more sensitive to Fas-induced hepatotoxicity and have delayed liver regeneration post-hepatectomy, with persistent TNF-α/IL6/STAT3 signaling [5]. In yeast, mutants with deletions of both reg1 and reg2 exhibit a severe growth defect, while reg2 single mutants have a wild-type phenotype [6].

In conclusion, Reg2 is essential for pancreatic islet compensation in response to aging and high-fat diet-induced obesity, and it also plays a crucial role in liver protection and regeneration. The study of Reg2-/-mouse models has provided valuable insights into its functions in glucose metabolism-related diseases and liver-related pathologies. In yeast, REG2 contributes to the regulation of growth through its interaction with other key proteins.