Modelagem do fenótipo de diabetes em Nauphoeta cinerea usando estreptozotocina: Foco no metabolismo da glicose no cérebro

• Ano de defesa: 2021
• Autor(a) principal: Olagoke, Olawande Chinedu
• Orientador(a): Rocha, João Batista Teixeira da
• Banca de defesa: Loreto, Elgion Lúcio da Silva, Folmer, Vanderlei, Puntel, Robson Luiz, Araújo , Daniel Mendes Pereira Ardisson de
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Universidade Federal de Santa Maria; Centro de Ciências Naturais e Exatas
• Programa de Pós-Graduação: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
• Departamento: Bioquímica
• País: Brasil
• Palavras-chave em Português: GLUT1; Sinalização de insulina; Caminho JNK; Caminho TOLL/NF-kB; Caminho UPD3/JAK/STAT; Antioxidantes; Proteínas ribossômicas; RNA-seq; Análise de transcriptoma
• Palavras-chave em Inglês: Insulin signaling; JNK pathway; TOLL/NF-kB pathway; UPD3/JAK/STAT pathway; Antioxidants; Ribosomal proteins; Transcriptome analysis
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/22168

The brain is highly dependent on adequate glucose catabolism, but changes in brain glucose transport are well documented in hyperglycemic conditions. Recent evidence of “hyperglycemic memory" further suggests that chronic exposure to hyperglycemia may predispose to deleterious alteration even after normal glycemic levels are restored. Therefore, it is important not only to try to maintain circulating glucose levels within the normal range, but also to avoid the lasting complications caused by chronic hyperglycemia. At the end of the 20th century, insect models (such as Drosophila melanogaster) began to be considered as important tools in the study of insulin-related human pathologies. Cockroaches have already been shown to be effective experimental organisms for neurobiology research, therefore, we herein explore brain energy metabolism using a known alkylating agent – streptozotocin – in Nauphoeta cinerea. First, we elucidate the biochemical and molecular changes resulting from acute exposure of cockroaches to streptozotocin (1 dose of 74 nmol or 740 nmol per g of bodymass). Streptozotocin caused an increase in glucose, mRNA levels of glucose transporter 1, thiobarbituric acid reactive substances, total glutathione S-transferase activity, and glutathione levels in head homogenates. Fat body glycogen, head triglyceride content and the reduction of MTT in head homogenates were diminished. Our results showed streptozotocin-induced alterations in the metabolism of glucose in N. cinerea, and we also highlight the evolutionary conservation of GLUT1 between N. cinerea and other insects. Secondly, we examined how streptozotocin-induced hyperglycemia in the CNS of N. Cinerea affects redox homeostasis and the expression of genes related to inflammatory response. We found an increase in mRNA levels of early growth response factor (EGR) and reaper (target genes of the c-Jun N terminal kinase pathway); TOLL1 (target gene of the Toll/NF-κB pathway); unpaired 3 (UPD 3) and suppressor of cytokine signaling at 36E Socs36E (activator and target gene of the UPD3/JAK/STAT pathway); superoxide dismutase and catalase (primary antioxidants) and GST sigma. There was no significant difference in the expression of PDGF -and VEGF -related factor 1 (PVF1), peroxiredoxin (PRX), thioredoxin (TRX) and GST delta. These changes in inflammation-related signaling and antioxidant enzyme activity are similar to changes observed in rodents and humans with hyperglycemia. Third, we showed transcriptional modifications that are similar to results of genome wide association studies in mammals and flies, especially the up regulation of the 40S ribosomal protein S6 and its signaling molecules. Low dose STZ treatment deregulated more genes than the high dose treatment, and there was a higher rate of up regulation than down regulation. We also identified the putative insulin signaling pathway of N. cinerea and observed a decrease in the transcription of components of the PI3K/AKT pathway, but target genes of the RAS, P38 and JNK MAPK cascade were up regulated. Structure-function elements were also similar between the MAPK genes of N. cinerea and other insects. Together, these data demonstrate that the cockroach N. cinerea can be used in the study of metabolic alterations caused by increased brain glucose levels.