241 research outputs found
Altered glucose homeostasis and hepatic function in obese mice deficient for both kinin receptor genes
The Kallikrein-Kinin System (KKS) has been implicated in several aspects of metabolism, including the regulation of glucose homeostasis and adiposity. Kinins and des-Arg-kinins are the major effectors of this system and promote their effects by binding to two different receptors, the kinin B2 and B1 receptors, respectively. To understand the influence of the KKS on the pathophysiology of obesity and type 2 diabetes (T2DM), we generated an animal model deficient for both kinin receptor genes and leptin (obB1B2KO). Six-month-old obB1B2KO mice showed increased blood glucose levels. Isolated islets of the transgenic animals were more responsive to glucose stimulation releasing greater amounts of insulin, mainly in 3-month-old mice, which was corroborated by elevated serum C-peptide concentrations. Furthermore, they presented hepatomegaly, pronounced steatosis, and increased levels of circulating transaminases. This mouse also demonstrated exacerbated gluconeogenesis during the pyruvate challenge test. The hepatic abnormalities were accompanied by changes in the gene expression of factors linked to glucose and lipid metabolisms in the liver. Thus, we conclude that kinin receptors are important for modulation of insulin secretion and for the preservation of normal glucose levels and hepatic functions in obese mice, suggesting a protective role of the KKS regarding complications associated with obesity and T2DM
Freqüência de aglutininas anti-Leptospira interrogans em eqüídeos, em Minas Gerais, 2003 a 2004
In vitro behaviour of Aspasia variegata, an epiphytic orchid from the Brazilian Cerrado
Combination of inoculation methods of Azospirilum brasilense with broadcasting of nitrogen fertilizer increases corn yield
Transitory increased blood pressure after upper airway surgery for snoring and sleep apnea correlates with the apnea-hypopnea respiratory disturbance index
Controle da leptospirose em bovinos de leite com vacina autógena em Santo Antônio do Monte, Minas Gerais
Reduced SLIT2 is associated with increased cell proliferation and arsenic trioxide resistance in acute promyelocytic Leukemia
The SLIT-ROBO axis plays an important role in normal stem-cell biology, with possible
repercussions on cancer stem cell emergence. Although the Promyelocytic Leukemia (PML) protein
can regulate SLIT2 expression in the central nervous system, little is known about SLIT2 in acute
promyelocytic leukemia. Hence, we aimed to investigate the levels of SLIT2 in acute promyelocytic
leukemia (APL) and assess its biological activity in vitro and in vivo. Our analysis indicated that
blasts with SLIT2high transcript levels were associated with cell cycle arrest, while SLIT2low APL
blasts displayed a more stem-cell like phenotype. In a retrospective analysis using a cohort of
patients treated with all-trans retinoic acid (ATRA) and anthracyclines, high SLIT2 expression was
correlated with reduced leukocyte count (p = 0.024), and independently associated with improved
overall survival (hazard ratio: 0.94; 95% confidence interval: 0.92–0.97; p < 0.001). Functionally,
SLIT2-knockdown in primary APL blasts and cell lines led to increased cell proliferation and resistance
to arsenic trioxide induced apoptosis. Finally, in vivo transplant of Slit2-silenced primary APL blasts
promoted increased leukocyte count (p = 0.001) and decreased overall survival (p = 0.002) compared
with the control. In summary, our data highlight the tumor suppressive function of SLIT2 in APL and
its deteriorating effects on disease progression when downregulated
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