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Chinese Medical Journal ; (24): 922-932, 2023.
Article in English | WPRIM | ID: wpr-980843


BACKGROUND@#Pancreatic β-cells elevate insulin production and secretion through a compensatory mechanism to override insulin resistance under metabolic stress conditions. Deficits in β-cell compensatory capacity result in hyperglycemia and type 2 diabetes (T2D). However, the mechanism in the regulation of β-cell compensative capacity remains elusive. Nuclear factor-Y (NF-Y) is critical for pancreatic islets' homeostasis under physiological conditions, but its role in β-cell compensatory response to insulin resistance in obesity is unclear.@*METHODS@#In this study, using obese ( ob/ob ) mice with an absence of NF-Y subunit A (NF-YA) in β-cells ( ob , Nf-ya βKO) as well as rat insulinoma cell line (INS1)-based models, we determined whether NF-Y-mediated apoptosis makes an essential contribution to β-cell compensation upon metabolic stress.@*RESULTS@#Obese animals had markedly augmented NF-Y expression in pancreatic islets. Deletion of β-cell Nf-ya in obese mice worsened glucose intolerance and resulted in β-cell dysfunction, which was attributable to augmented β-cell apoptosis and reactive oxygen species (ROS). Furthermore, primary pancreatic islets from Nf-ya βKO mice were sensitive to palmitate-induced β-cell apoptosis due to mitochondrial impairment and the attenuated antioxidant response, which resulted in the aggravation of phosphorylated c-Jun N-terminal kinase (JNK) and cleaved caspase-3. These detrimental effects were completely relieved by ROS scavenger. Ultimately, forced overexpression of NF-Y in INS1 β-cell line could rescue palmitate-induced β-cell apoptosis, dysfunction, and mitochondrial impairment.@*CONCLUSION@#Pancreatic NF-Y might be an essential regulator of β-cell compensation under metabolic stress.

Rats , Mice , Animals , Reactive Oxygen Species/metabolism , Diabetes Mellitus, Type 2/metabolism , Insulin Resistance , Insulin , Insulin-Secreting Cells/metabolism , Apoptosis , Stress, Physiological , Transcription Factors/metabolism , Palmitates/pharmacology , Obesity/metabolism
Acta cir. bras ; 26(4): 274-278, July-Aug. 2011. ilus
Article in English | LILACS | ID: lil-594346


PURPOSE: To quantify the amount of bone formation in the calvarial region of Wistar rats after craniotomy using bone wax as a haemostatic agent. METHODS: Surgery to produce bilateral, symmetric, full-thickness cranial defects (area: 18 mm²) was performed in eight animals. The right side of the cranium remained open and the edges of the left side osseous defect was covered with bone wax. Calvaria were imaged immediately after surgery and 12 weeks postoperatively by computerized tomography. The areas of the bone defects were measured in three-dimensional images using Magics 13.0 (Materialise-Belgic, software CAD). RESULTS: The average amount of bone formation on the left and right side respectively was 4.85 mm² and 8.16 mm². Statistically significant differences between the amount of bone formation on the left and right sides were seen. CONCLUSIONS: Bone wax significantly diminishes the rate of bone formation in calvarial defects in a rat model.

OBJETIVO: Quantificar a formação óssea da região da calvaria de ratos Wistar submetidos à craniotomia com a utilização de cera de osso como agente hemostático. MÉTODOS: Cirurgia para realizar um defeito ósseo craniano bilateral, simétrico (área: 18 mm²) e com espessura total foi realizado em oito animais. O lado direito do crânio permaneceu aberto e as extremidades do defeito ósseo do lado esquerdo foram recobertas com cera de osso. O crânio foi submetido à avaliação radiológica imediatamente após a cirurgia e 12 semanas após a cirurgia com a utilização de tomografia computadorizada. As áreas dos defeitos ósseos foram medidas através de imagens tridimensionais e utilizando o programa de computador Magics 13.0 (Materialise-Belgic, software CAD). RESULTADOS: A quantidade média de formação óssea no lado esquerdo e direito foi respectivamente de 4.85 mm² e 8.16 mm². Diferença estatisticamente significante foi observada entre o lado direito e esquerdo. CONCLUSÕES: A cera de osso diminuiu significativamente a formação óssea nos defeitos ósseos em modelo animal.

Animals , Male , Rats , Hemostatics/pharmacology , Osteogenesis/drug effects , Palmitates/pharmacology , Skull/surgery , Waxes/pharmacology , Wound Healing/drug effects , Cephalometry , Disease Models, Animal , Inflammation/pathology , Osteogenesis/physiology , Photomicrography , Rats, Wistar , Skull/injuries , Skull , Time Factors , Tomography, X-Ray Computed , Wound Healing/physiology
Braz. j. med. biol. res ; 31(11): 1421-4, Nov. 1998. graf
Article in English | LILACS | ID: lil-224476


Oral tolerance is a phenomenon that may occur in animals exposed to protein antigens for the first time by the oral route. They become unable to produce immune responses at the levels normally observed when they are immunized parenterally with antigen in the presence of adjuvants. Lipids have been used as adjuvants for both parenteral and oral immunization. In the present study we coupled ovalbumin with palmitate residues by incubating the protein with the N-hydroxysuccinimide palmitate ester and tested the preparation for its ability to induce oral tolerance. This was performed by giving 20 mg of antigen to mice by the oral route 7 days prior to parenteral immunization in the presence of Al(OH)3. Mice were bled one week after receiving a booster that was given 2 weeks after primary immunization. Specific antibodies were detected by ELISA. Despite the fact that the conjugates are as immunogenic as the unmodified protein when parenterally injected in mice, they failed to induce oral tolerance. This discrepancy could be explained by differences in the intestinal absorption of the two forms of the antigen. In fact, when compared to the non-conjugated ovalbumin, a fast and high absorption of the lipid-conjugated form of ovalbumin was observed by "sandwich" ELISA.

Animals , Mice , Immune Tolerance , Ovalbumin/pharmacology , Palmitates/pharmacology , Serine Proteinase Inhibitors/pharmacology , Ovalbumin/immunology , Palmitates/immunology , Serine Proteinase Inhibitors/immunology