Reg2, also known as regenerating islet-derived 2 (Reg II, human ortholog Reg1B), is a protein-coding gene. In mammals, it functions as a trophic factor that stimulates β-cell replication, resists islet destruction, and is involved in maintaining pancreatic β-cell mass and function for normal insulin production and glucose homeostasis [1,2]. In yeast (Saccharomyces cerevisiae), REG2 encodes a type 1 protein phosphatase-binding protein that functions with Reg1p and the Snf1 protein kinase to regulate growth [3].

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 a significantly decreased islet β-cell ratio and serum insulin level. Also, after young mice are fed a high-fat diet (HFD) for 19 weeks, Reg2-/-mice show diminished islet mass expansion and serum insulin level, along with a decline in the rate of individual β-cell proliferation [2]. These results from the KO mouse model indicate that normal expression of Reg2 is required for appropriate pancreatic islet proliferation and expansion in response to obesity and aging.

In conclusion, Reg2 plays a crucial role in maintaining pancreatic islet function, especially in compensating for the effects of aging and HFD-induced obesity. The use of Reg2 KO mouse models has provided valuable insights into the role of Reg2 in glucose homeostasis-related diseases, highlighting its importance in understanding the mechanisms underlying diabetes-related islet-cell function decline.