17beta-Estradiol Modulates Apoptosis in Pancreatic beta-Cells by Specific Involvement of the Sulfonylurea Receptor (SUR) Isoform SUR1 Export

@article{citeulike:4219773, abstract = {Apoptosis of pancreatic {beta}-cells is an important factor in the pathophysiology of diabetes. Previously, we have shown that the "phytoestrogen" resveratrol can induce {beta}-cell apoptosis dependent on the expression of sulfonylurea receptor (SUR) 1, the regulatory subunit of pancreatic ATP-sensitive K+ channels. Here, we investigate whether 17{beta}-estradiol also influences {beta}-cell apoptosis in a SUR1-dependent manner. Therefore, islets from wild type or SUR1 knock-out mice, clonal {beta}-cells, or HEK293 cells expressing different SUR forms were treated with 17{beta}-estradiol or estrone. Different apoptotic parameters were determined and estrogen binding to SUR was analyzed. In murine islets, 17{beta}-estradiol treatment resulted in significant apoptotic changes, which in their nature (either apoptotic or anti-apoptotic) were dependent on the age of the animal. These effects were not observed in SUR1 knock-out mice. Furthermore, 17{beta}-estradiol, which specifically binds to SUR, induced enhanced apoptosis in SUR1-expressing HEK293 cells and clonal {beta}-cells, whereas apoptosis in recombinant cells expressing SUR2A or SUR2B (cardiac or vascular SUR-isoforms) or sham-transfected control cells was significantly lower. The apoptotic potency of 17{beta}-estradiol was much higher than that of resveratrol or estrone. SUR1-specific 17{beta}-estradiol-induced apoptosis was either abolished by the mutation M1289T in transmembrane helix 17 of SUR1 or clearly enhanced by two mutations in nucleotide binding fold 2 (R1379C, R1379L). In conclusion, 17{beta}-estradiol treatment modulates {beta}-cell apoptosis under specific involvement of SUR1 in an age-dependent manner. 17{beta}-Estradiol-induced apoptosis can be influenced by certain SUR1 mutations. These findings may contribute to the understanding of pathophysiological changes in {beta}-cell mass and could, for instance, provide interesting aspects concerning the etiology of gestational diabetes. 10.1074/jbc.M807638200}, author = {Ackermann, Stefanie and Hiller, Sabrina and Osswald, Hartmut and Losle, Martina and Grenz, Almut and Hambrock, Annette}, citeulike-article-id = {4219773}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M807638200}, citeulike-linkout-1 = {http://www.jbc.org/cgi/content/abstract/284/8/4905}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19095654}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19095654}, day = {20}, doi = {10.1074/jbc.M807638200}, journal = {J. Biol. Chem.}, keywords = {apoptosis, estradiol, insulin}, month = {February}, number = {8}, pages = {4905--4913}, posted-at = {2009-03-25 15:00:10}, priority = {2}, title = {17{beta}-Estradiol Modulates Apoptosis in Pancreatic {beta}-Cells by Specific Involvement of the Sulfonylurea Receptor (SUR) Isoform SUR1}, url = {http://dx.doi.org/10.1074/jbc.M807638200}, volume = {284}, year = {2009} }

TY - JOUR ID - citeulike:4219773 L3 - citeulike-article-id:4219773 N2 - Apoptosis of pancreatic {beta}-cells is an important factor in the pathophysiology of diabetes. Previously, we have shown that the "phytoestrogen" resveratrol can induce {beta}-cell apoptosis dependent on the expression of sulfonylurea receptor (SUR) 1, the regulatory subunit of pancreatic ATP-sensitive K+ channels. Here, we investigate whether 17{beta}-estradiol also influences {beta}-cell apoptosis in a SUR1-dependent manner. Therefore, islets from wild type or SUR1 knock-out mice, clonal {beta}-cells, or HEK293 cells expressing different SUR forms were treated with 17{beta}-estradiol or estrone. Different apoptotic parameters were determined and estrogen binding to SUR was analyzed. In murine islets, 17{beta}-estradiol treatment resulted in significant apoptotic changes, which in their nature (either apoptotic or anti-apoptotic) were dependent on the age of the animal. These effects were not observed in SUR1 knock-out mice. Furthermore, 17{beta}-estradiol, which specifically binds to SUR, induced enhanced apoptosis in SUR1-expressing HEK293 cells and clonal {beta}-cells, whereas apoptosis in recombinant cells expressing SUR2A or SUR2B (cardiac or vascular SUR-isoforms) or sham-transfected control cells was significantly lower. The apoptotic potency of 17{beta}-estradiol was much higher than that of resveratrol or estrone. SUR1-specific 17{beta}-estradiol-induced apoptosis was either abolished by the mutation M1289T in transmembrane helix 17 of SUR1 or clearly enhanced by two mutations in nucleotide binding fold 2 (R1379C, R1379L). In conclusion, 17{beta}-estradiol treatment modulates {beta}-cell apoptosis under specific involvement of SUR1 in an age-dependent manner. 17{beta}-Estradiol-induced apoptosis can be influenced by certain SUR1 mutations. These findings may contribute to the understanding of pathophysiological changes in {beta}-cell mass and could, for instance, provide interesting aspects concerning the etiology of gestational diabetes. 10.1074/jbc.M807638200 IS - 8 JF - J. Biol. Chem. EP - 4913 TI - 17{beta}-Estradiol Modulates Apoptosis in Pancreatic {beta}-Cells by Specific Involvement of the Sulfonylurea Receptor (SUR) Isoform SUR1 VL - 284 SP - 4905 KW - apoptosis KW - estradiol KW - insulin AU - Ackermann, Stefanie AU - Hiller, Sabrina AU - Osswald, Hartmut AU - Losle, Martina AU - Grenz, Almut AU - Hambrock, Annette PY - 2009/02/20/ UR - http://dx.doi.org/10.1074/jbc.M807638200 ER -