A low protein diet alters gene expression in rat pancreatic islets

Insulin secretion is regulated mainly by circulating nutrients, particularly glucose, and is also modulated by hormonal and neuronal inputs. Nutritional alterations during fetal and early postnatal periods, induced by either low protein or energy-restricted diets, produce beta-cell dysfunction. As a consequence, insulin secretion in response to different secretagogues is reduced, as is the number of beta-cells and the size and vascularization of islets. In this study, we used a cDNA macroarray technique and RT-PCR to assess the pattern of gene expression in pancreatic islets from rats fed isocaloric low (6 g/100 g, LP) and normal (17 g/100 g, NP) protein diets, after weaning. Thirty-two genes related to metabolism, neurotransmitter receptors, protein trafficking and targeting, intracellular kinase network members and hormones had altered expression (up- or down-regulated). RT-PCR confirmed the macroarray results for five selected genes, i.e., clusterin, secretogranin II precursor, eukaryotic translation initiation factor 2, phospholipase A(2) and glucose transporter. Thus, cDNA macroarray analysis revealed significant changes in the gene expression pattern in rats fed a low protein diet after weaning. The range of proteins affected indicated that numerous mechanisms are involved in the intracellular alterations in the endocrine pancreas, including impaired glucose-induced insulin secretion.