PLX020948

GSE114207: Mice Harboring the Human SLC30A8 R138X Loss-of-Function Mutation Have Increased Insulin Secretory Capacity

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

SLC30A8 encodes a zinc transporter that is primarily expressed in the pancreatic islets of Langerhans. In beta-cells it transports zinc into insulin-containing secretory granules. Loss-of-function (LOF) mutations in SLC30A8 protect against type 2 diabetes in humans. In this study, we generated a mouse model carrying one of the most common human LOF mutations for SLC30A8, R138X. The R138X mice had normal body weight, glucose tolerance and pancreatic beta-cell mass. Interestingly, in hyperglycemic conditions induced by the insulin receptor antagonist S961, the R138X mice showed a 50% increase in insulin secretion. This effect was not associated with enhanced beta-cell proliferation or beta-cell mass. Our data suggest that the SLC30A8 R138X LOF mutation in humans may protect from type 2 diabetes in part by increasing the capacity of beta-cells to secrete insulin. SOURCE: Yurong Xin (yurong.xin@regeneron.com) - Regeneron Pharmaceuticals, Inc.