title: Metabolic memory of ß-cells controls insulin secretion and is mediated by CaMKII.
abstract: 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.
authors.affiliation: 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.
authors.forename: Gustavo Jorge Dos
authors.initials: GJ
authors.lastname: Santos
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, CEP 13083-865, Brazil.
authors.forename: Sandra Mara
authors.initials: SM
authors.lastname: Ferreira
authors.affiliation: 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 Cell and Developmental Biology, Biomedical and Biological Sciences Institute of the University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Ortis
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, CEP 13083-865, Brazil.
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: Rezende
authors.affiliation: Department of Surgery and Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Chengyang
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Surgery and Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Naji
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, CEP 13083-865, Brazil.
authors.forename: Everardo Magalhães
authors.initials: EM
authors.lastname: Carneiro
authors.affiliation: 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.
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Kaestner
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, CEP 13083-865, Brazil.
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Boschero
keywords: CaMKII; Insulin secretion; Metabolic memory