Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Protein restriction in the early stages of life can result in several changes in pancreatic function. These alterations include documented reductions in insulin secretion and in cytoplasmic calcium concentration [Ca2+](i). However, the mechanisms underlying these changes have not been completely elucidated and may result, in part, from alterations in signaling pathways that potentiate insulin secretion in the presence of glucose. Our findings suggest that protein restriction disrupts the insulin secretory synergism between Cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and Ca2+ -dependent protein kinase C (PKC) in isolated islets. Western blot analysis demonstrated reduced levels of both phospho-cAMP response element-binding protein (phospho-CREB) at Ser-133 and substrates phosphorylated by PKCs (Phospho-(Ser) PKC substrate), suggesting that PICA and PKC activity was impaired in islets from rats fed a low-protein diet (LP). cAMP levels and global Ca2+ entry were also reduced in LP islets. In summary, our findings showed that protein restriction altered the crosstalk between PICA and PKC signaling pathways, resulting in the alteration of secretory synergism in isolated islets. (C) 2015 Elsevier Inc. All rights reserved.265 556562Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)