Transcriptomics

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


ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE114207 | GEO | 2018/11/01

REPOSITORIES: GEO

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