| First Author | Kleiner S | Year | 2018 |
| Journal | Proc Natl Acad Sci U S A | Volume | 115 |
| Issue | 32 | Pages | E7642-E7649 |
| PubMed ID | 30038024 | Mgi Jnum | J:264368 |
| Mgi Id | MGI:6194813 | Doi | 10.1073/pnas.1721418115 |
| Citation | Kleiner S, et al. (2018) Mice harboring the human SLC30A8 R138X loss-of-function mutation have increased insulin secretory capacity. Proc Natl Acad Sci U S A 115(32):E7642-E7649 |
| abstractText | 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 knockin 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 mass. Our data suggest that the SLC30A8 R138X LOF mutation may exert beneficial effects on glucose metabolism by increasing the capacity of beta-cells to secrete insulin under hyperglycemic conditions. |
