Influência do peptídeo 1 semelhante ao glucagon (GLP-1) sobre a expressão do pancreato-duodenal homeobox 1 (Pdx-1) e o conteúdo e secreção de insulina em ilhotas de ratas adultas submetidas à restrição proteica

Abstract

Protein restriction has been associated with the decrease of insulin content and insulin secretory capacity in rodents, which is followed by reduction of the pancreatic-duodenal homeobox 1 (PDX-1) expression, a transcription factor modulated by glucagon-like peptide 1. In order to evaluate whether the insulin content and secretion as well as the transcription of the Pdx-1 gene in rat dams fed a protein-restricted diet are modulated by GLP-1, female Wistar rats were divided into four groups on the basis of their type of diet and treatment with GLP-1 receptor agonist: 1) Control; 2) Control Agonist; 3) Hypoproteic; 4) Hypoproteic Agonist. Plasma concentrations of GLP-1 were similar in the four studied groups. Rats that were fed low-protein diets had lower body weight, hypoalbuminemia, hypoproteinemia, areas under the glucose and insulin curves during oral glucose tolerance test, HOMA-IR, HOMA-BETA, and insulin-secretory response to basal, physiological and supraphysiological glucose concentrations than the control rats regardless the treatment with agonist. In the post-absorptive state, insulin did not differ between the groups and the glucose level in blood was higher for groups treated with agonist regardless their previous nutritional status. Treatment with agonist increased the mRNA expression of PDX-1 in the Hypoproteicgroup, however it decreased in the Control group. Therefore, GLP-1 influences PDX-1 transcription, but this effect was not enough to stimulate insulin content and secretion in pancreatic islets from rat dams fed a low-protein diet.