Slc30a8-flox Mouse

Slc30a8, which encodes the zinc transporter ZnT8, is a gene mainly expressed in the secretory granules of pancreatic islet α and β cells. It transports zinc from the cytoplasm to insulin secretory granules in pancreatic β -cells, playing a crucial role in the proper storage, secretion, and action of insulin, thus being important for glucose homeostasis [2,4].

In mice with Slc30a8 knockout, insulin secretion from isolated islets is often increased, but they usually show impaired glucose tolerance and lower circulating insulin. This may be due to increased hepatic clearance caused by lower local zinc levels or less efficient insulin action on target tissues [1]. Moreover, a loss-of-function variant (R138X) study in mice found that homozygous mutant mice had a significant decrease in total islet zinc, while heterozygous mice had a marked increase in endocrine and exocrine zinc and manganese content, suggesting a complex role of Slc30a8 in pancreatic metal homeostasis and insulin secretion [3].

In conclusion, Slc30a8 is essential for maintaining normal insulin-related functions and glucose homeostasis. Gene-knockout mouse models have revealed its complex role in processes such as insulin secretion and pancreatic metal ion distribution, which is closely associated with type 2 diabetes and other related diseases, providing important insights into understanding the disease mechanisms [1,2,3].