Participação do Peptídeo semelhante ao Glucagon-1 (GLP-1) na modulação de mecanismos que regulam a massa de células β pancreáticas em ratas adultas submetidas à restrição proteica na vida intrauterina e lactação e recuperadas após o desmame

Abstract

Protein restriction in early life reduces permanently the β-cell mass, due to increase of apoptosis and reduction of proliferation. The glucagon-like peptide-1 (GLP-1) stimulates the replication and neogenesis, and reduces apoptosis, Increasing β-cell mass. We evaluated the GLP-1 intra-islet production and its modulator effects on apoptosis, replication and neogenesis of -cells in adult rats submitted to protein restriction in critical phases of development. Female adult control non treated or treated rats (NTC and TC, respectively), consisting of offspring born to and suckled by mothers fed a control diet, maintained with the same diet until 90 d of age and receiving saline or exendin-4; and recovered non treated or treated rats (NTR and TR, respectively) consisting of offspring born to and suckled by mothers fed a low-protein diet, maintained with control diet after weaning diet until 90 d of age and receiving saline or exendin-4 . Saline or exendin-4 were administered for 15d from 75 d of age. The -cell mass was lower in the recovered than in the control groups. Exendin-4 increased the -cells mass, regardless of nutritional status. Colocalization of GLP-1/Glucagon was higher in NTR than in NTC rats, and in the TR group compared to TC group. The frequency of cleaved caspase-3- labeled cells was higher in NTR group than in NTC group and was similar in the TR and TC groups. Regardless of treatment with exendin-4, the Ki67-labeled cells frequency and -catenin/DAPI colocalization were higher in the recovered groups. Exendin-4 increased the area of endocrine cell clusters, -catenina/DAPI and FoxO1/DAPI colocalizations

regardless of nutritional status. Thus, protein restriction in the early life increased intra- islet GLP-1 production and the -cell proliferation possibly mediated by the -catenin

pathway.