Reduced pancreatic beta-cell mass is associated with decreased FoxO1 and Erk1/2 protein phosphorylation in low-protein malnourished rats

Autor(es)

Rafacho, A. ^[1] ; Giozzet, V. A. G. ^[2] ; Boschero, A. C. ^[2] ; Abrantes, J. L. F. ^[2] ; Cestari, T. M. ^[3] ; Carneiro, E. M. ^[2] ; Bosqueiro, J. R. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Paulista, Fac Ciencias, Dept Educ Fis, BR-17033360 Bauru, SP - Brazil

^[2] Univ Estadual Campinas, Inst Biol, Dept Anat Biol Celular & Fisiol, Campinas, SP - Brazil

^[3] Univ Sao Paulo, Dept Ciencias Biol, Fac Odontol Bauru, Bauru, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 42, n. 10, p. 935-941, OCT 2009.
• Citações Web of Science: 7

Resumo

A low-protein diet leads to functional and structural pancreatic islet alterations, including islet hypotrophy. Insulin-signaling pathways are involved in several adaptive responses by pancreatic islets. We determined the levels of some insulin-signaling proteins related to pancreatic islet function and growth in malnourished rats. Adult male Wistar rats (N = 20 per group) were fed a 17% protein (normal-protein diet; NP) or 6% protein (low-protein diet; LP), for 8 weeks. At the end of this period, blood glucose and serum insulin and albumin levels were measured. The morphometric parameters of the endocrine pancreas and the content of some proteins in islet lysates were determined. The beta-cell mass was significantly reduced (congruent to 65%) in normoglycemic but hypoinsulinemic LP rats compared to NP rats. Associated with these alterations, a significant 30% reduction in insulin receptor substrate-1 and a 70% increase in insulin receptor substrate-2 protein content were observed in LP islets compared to NP islets. The phosphorylated serine-threonine protein kinase (pAkt)/Akt protein ratio was similar in LP and NP islets. The phosphorylated forkhead-O1 (pFoxO1)/FoxO1 protein ratio was decreased by 43% in LP islets compared to NP islets (P < 0.05). Finally, the ratio of phosphorylated-extracellular signal-related kinase 1/2 (pErk1/2) to total Erk1/2 protein levels was decreased by 71% in LP islets compared to NP islets (P < 0.05). Therefore, the reduced beta-cell mass observed in LP rats is associated with the reduction of phosphorylation in mitogenic-related signals, FoxO1 and Erk proteins. The cause/effect basis of this association remains to be determined. (AU)

• Processo FAPESP: 04/11684-9 - Avaliação dos efeitos de diferentes concentrações da dexametasona sobre parâmetros fisiológicos de Ilhotas pancreáticas
• Beneficiário: Alex Rafacho
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 03/10829-0 - Análise das ações da dexametasona sobre a secreção de insulina, parâmetros bioquímicos e moleculares em ratos submetidos a restrição protéica
• Beneficiário: Vanessa Aparecida Gonçalves Giozzet
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto