Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes. Export

@article{citeulike:387175, abstract = {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.}, address = {The Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.}, author = {Koster, J. C. and Marshall, B. A. and Ensor, N. and Corbett, J. A. and Nichols, C. G.}, citeulike-article-id = {387175}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/10761930}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=10761930}, comment = {Referenced by Colin Nichols in a lecture at Wash U 2005-11-09}, day = {17}, issn = {0092-8674}, journal = {Cell}, keywords = {beta\_cell, channels, diabetes, i-katp, ion\_channels, k, neonatal, pancreas, potassium}, month = {March}, number = {6}, pages = {645--654}, posted-at = {2005-11-10 14:10:35}, priority = {2}, title = {Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/10761930}, volume = {100}, year = {2000} }

TY - JOUR ID - citeulike:387175 L3 - citeulike-article-id:387175 N2 - 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. IS - 6 JF - Cell SN - 0092-8674 AD - The Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. EP - 654 TI - Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes. VL - 100 SP - 645 KW - beta_cell KW - channels KW - diabetes KW - i-katp KW - ion_channels KW - k KW - neonatal KW - pancreas KW - potassium N1 - Referenced by Colin Nichols in a lecture at Wash U 2005-11-09 AU - Koster, JC AU - Marshall, BA AU - Ensor, N AU - Corbett, JA AU - Nichols, CG PY - 2000/03/17/ UR - http://view.ncbi.nlm.nih.gov/pubmed/10761930 ER -