Low-protein diet disrupts the crosstalk between the PKA and PKC signaling pathways in isolated pancreatic islets.
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 [Ca(2+)]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 Ca(2+)-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 PKA and PKC activity was impaired in islets from rats fed a low-protein diet (LP). cAMP levels and global Ca(2+) entry were also reduced in LP islets. In summary, our findings showed that protein restriction altered the crosstalk between PKA and PKC signaling pathways, resulting in the alteration of secretory synergism in isolated islets.
Department of Pharmaceutical Sciences, Federal University of Pernambuco, 50740-600, Recife, PE, Brazil.
Bruno Rodrigo da Silva
BR
Lippo
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-865, SP, Brazil.
Thiago Martins
TM
Batista
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-865, SP, Brazil.
Luiz Fernando
LF
de Rezende
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-865, SP, Brazil.
Ana Paula
AP
Cappelli
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-865, SP, Brazil.
Rafael Ludemann
RL
Camargo
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-865, SP, Brazil.
Renato Chaves Souto
RC
Branco
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-865, SP, Brazil.
Helena Cristina Barbosa
HC
Sampaio
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-865, SP, Brazil.
André Otávio Peres
AO
Protzek
Department of Physiology and Pharmacology, Federal University of Pernambuco, 50670-901, Recife, PE, Brazil.
Maria Inês
MI
Wanderley
Department of Food and Nutrition, Faculty of Nutrition, Federal University of Mato Grosso, 78060-900, Cuiabá, MT, Brazil.
Vanessa Cristina
VC
Arantes
Multidisciplinary Center for Biological Research, Unity of Transgenesis, State University of Campinas, 13083-877, SP, Brazil.
Marcus Alexandre Finzi
MA
Corat
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-865, SP, Brazil.
Everardo Magalhães
EM
Carneiro
Department of Physiology and Pharmacology, Federal University of Pernambuco, 50670-901, Recife, PE, Brazil.
Daniel Pedro
DP
Udrisar
Department of Pharmaceutical Sciences, Federal University of Pernambuco, 50740-600, Recife, PE, Brazil; Department of Physiology and Pharmacology, Federal University of Pernambuco, 50670-901, Recife, PE, Brazil.
Almir Gonçalves
AG
Wanderley
Department of Physiology and Pharmacology, Federal University of Pernambuco, 50670-901, Recife, PE, Brazil. Electronic address: fabiano.fdino@gmail.com.
Fabiano
F
Ferreira
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D018753:Diet, Protein-Restricted; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C
Crosstalk; Insulin secretion; Low-protein diet; PKA; PKC