Picard Frédéric, Wanatabe Mitsuhiro, Schoonjans Kristina, Lydon John, O'Malley Bert W, Auwerx Johan
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche ScientifiqueInstitut National de la Santé et de la Recherche MédicalUniversité Louis Pasteur, 67404 Illkirch, France.
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15644-8. doi: 10.1073/pnas.202612199. Epub 2002 Nov 15.
Gestational diabetes coincides with elevated circulating progesterone levels. We show that progesterone accelerates the progression of diabetes in female dbdb mice. In contrast, RU486, an antagonist of the progesterone receptor (PR), reduces blood glucose levels in both female WT and dbdb mice. Furthermore, female, but not male, PR-- mice had lower fasting glycemia than PR++ mice and showed higher insulin levels on glucose injection. Pancreatic islets from female PR-- mice were larger and secreted more insulin consequent to an increase in beta-cell mass due to an increase in beta-cell proliferation. These findings demonstrate an important role of progesterone signaling in insulin release and pancreatic function and suggest that it affects the susceptibility to diabetes.
妊娠期糖尿病与循环孕酮水平升高同时出现。我们发现孕酮会加速雌性dbdb小鼠糖尿病的进展。相比之下，孕酮受体（PR）拮抗剂RU486可降低雌性野生型和dbdb小鼠的血糖水平。此外，雌性而非雄性的PR--小鼠空腹血糖水平低于PR++小鼠，并且在注射葡萄糖后胰岛素水平更高。雌性PR--小鼠的胰岛更大，由于β细胞增殖增加导致β细胞质量增加，从而分泌更多胰岛素。这些发现证明了孕酮信号在胰岛素释放和胰腺功能中起着重要作用，并表明它会影响糖尿病易感性。
