Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, CEP 13083-865, Brazil ; Department of Genetics and Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine, 12-126 Translational Research Center, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA.
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, CEP 13083-865, Brazil.
Mol Metab. 2014 Apr 15;3(4):484-9. doi: 10.1016/j.molmet.2014.03.011. eCollection 2014 Jul.
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) functions both in regulation of insulin secretion and neurotransmitter release through common downstream mediators. Therefore, we hypothesized that pancreatic ß-cells acquire and store the information contained in calcium pulses as a form of "metabolic memory", just as neurons store cognitive information. To test this hypothesis, we developed a novel paradigm of pulsed exposure of ß-cells to intervals of high glucose, followed by a 24-h consolidation period to eliminate any acute metabolic effects. Strikingly, ß-cells exposed to this high-glucose pulse paradigm exhibited significantly stronger insulin secretion. This metabolic memory was entirely dependent on CaMKII. Metabolic memory was reflected on the protein level by increased expression of proteins involved in glucose sensing and Ca(2+)-dependent vesicle secretion, and by elevated levels of the key ß-cell transcription factor MAFA. In summary, like neurons, human and mouse ß-cells are able to acquire and retrieve information.
钙/钙调蛋白依赖性蛋白激酶 II（CaMKII）通过共同的下游介质在调节胰岛素分泌和神经递质释放中发挥作用。因此，我们假设胰腺β细胞将钙脉冲中包含的信息作为“代谢记忆”进行获取和存储，就像神经元存储认知信息一样。为了验证这一假设，我们开发了一种新的β细胞脉冲暴露范式，即β细胞间歇性暴露于高葡萄糖环境中，随后进行 24 小时的巩固期以消除任何急性代谢效应。令人惊讶的是，暴露于这种高葡萄糖脉冲范式的β细胞表现出明显更强的胰岛素分泌。这种代谢记忆完全依赖于 CaMKII。代谢记忆在蛋白质水平上表现为参与葡萄糖感应和 Ca2+依赖性囊泡分泌的蛋白质表达增加，以及关键的β细胞转录因子 MAFA 水平升高。总之，与神经元一样，人和鼠的β细胞能够获取和检索信息。
