The role of Palmitate in CaMKII - dependent metabolic memory formation

• Grant number: 12/18818-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2012
• End date: November 30, 2013
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Luiz Fernando de Rezende
• Grantee: Ariane Cristina de Almeida Dias
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 11/09012-6 - Molecular mechanisms involved in the dysfunction and death of pancreatic beta cells in Diabetes Mellitus: strategies for the prevention of islet dysfunction and for islet mass recuperation in different cellular and animal models, AP.TEM

Abstract

Calcium ion (Ca2+) acts as a cell signaling mediator in eukaryotic cells, controlling many functions such as proliferation, gene expression, apoptosis, and exocytosis. Calcium-calmodulin-dependent Kinase II (CaMKII), is a multifunctional protein that is intrinsically inhibited in low calcium environments thanks to its auto-inhibitory properties. After a peak in intracellular calcium levels, there is an increase in the formation of calcium-calmodulin complex, which then binds to CaMKII exposing its catalytic site. This mechanism allows CaMKII to maintain its auto-phosphorylation and activity independently of the calcium-CaM complex, thus extending its actions and the effects initially generated by calcium. In this context, palmitate is a long-chain saturated fatty acid highly prevalent in mammals, and in particular, in pancreatic islets ²-cells, such as MIN6 cell lines. In MIN6 cells, palmitate hinders glucose-induced CaMKII phosphorylation while increasing glucose-stimulated insulin secretion (GSIS). Given that, the aim of the present project is to investigate the possibility that palmitate is involved in the formation of a long-term action of calcium effects over GSIS through CaMKII.(AU)