| First Author | Koster JC | Year | 2000 |
| Journal | Cell | Volume | 100 |
| Issue | 6 | Pages | 645-54 |
| PubMed ID | 10761930 | Mgi Jnum | J:61172 |
| Mgi Id | MGI:1354522 | Doi | 10.1016/s0092-8674(00)80701-1 |
| Citation | Koster JC, et al. (2000) Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes. Cell 100(6):645-54 |
| abstractText | A paradigm for control of insulin secretion is that glucose metabolism elevates cytoplasmic [ATP]/[ADP] in beta cells, closing K(ATP) channels and causing depolarization, Ca2+ entry, and insulin release. Decreased responsiveness of K(ATP) channels to elevated [ATP]/[ADP] should therefore lead to decreased insulin secretion and diabetes. To test this critical prediction, we generated transgenic mice expressing beta cell K(ATP) channels with reduced ATP sensitivity. Animals develop severe hyperglycemia, hypoinsulinemia, and ketoacidosis within 2 days and typically die within 5. Nevertheless, islet morphology, insulin localization, and alpha and beta cell distributions were normal (before day 3), pointing to reduced insulin secretion as causal. The data indicate that normal K(ATP) channel activity is critical for maintenance of euglycemia and that overactivity can cause diabetes by inhibiting insulin secretion. |
