ABCC8, which encodes the sulfonylurea receptor 1 (SUR1), is a key gene involved in regulating insulin secretion. The protein it encodes, along with inward-rectifier potassium ion channel (Kir6.2), forms the ATP-sensitive potassium (KATP) channel in the plasma membranes of pancreatic β-cells, a crucial component of the glucose-stimulated insulin secretion pathway [1,2,3,5,6,7].

Mutations in ABCC8 can cause a variety of phenotypes related to dysregulated insulin secretion. Inactivating mutations lead to oversecretion of insulin, resulting in congenital hyperinsulinism, while activating mutations cause diabetes [1]. ABCC8-related diabetes can present as neonatal diabetes mellitus, non-neonatal diabetes mellitus (ABCC8-NNDM), or Maturity-Onset Diabetes of the Young 12 (MODY12) [1,3,4,7]. The phenotypes of ABCC8-NNDM are variable, and patients may have a relatively high risk of microvascular complications [3]. In MODY12, the 55 reported ABCC8 variants show large clinical heterogeneity, with HbA1c at diagnosis ranging from 5% to 14% and age at diagnosis from 2 to 53 years [4]. Some patients with ABCC8 gene variants can successfully switch from insulin to sulphonylurea therapy [9]. Additionally, in glioma, high ABCC8 mRNA expression is associated with longer survival and can predict sensitivity to temozolomide chemotherapy [8].

In conclusion, ABCC8 is essential for the normal regulation of insulin secretion through its role in forming the KATP channel in pancreatic β-cells. Genetic mutations in ABCC8 are strongly associated with various forms of diabetes, highlighting its significance in diabetes-related research. Understanding the functions of ABCC8 through genetic models can provide insights into the mechanisms of insulin-related diseases and potentially guide more targeted treatment strategies.