Browsing by Author "Conde, S.V."
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- Insulin resistance is associated with tissue-specific regulation of HIF-1α and HIF-2α during mild chronic intermittent hypoxiaPublication . Sacramento, J.F.; Ribeiro, M.J.; Rodrigues, T.; Guarino, Maria Pedro; Diogo, L.N.; Seiça, R.; Monteiro, E.C.; Matafome, P.; Conde, S.V.Chronic intermittent hypoxia (CIH) is a feature of obstructive sleep apnea (OSA). Whereas clinical stud-ies have demonstrated the association between OSA and insulin resistance, the molecular mechanismsbehind it are still unknown. Herein we investigated the effect of mild CIH on insulin sensitivity and weevaluated the changes in insulin and HIF signaling pathways that occur in CIH-induced insulin resistance.We showed that mild CIH obtained by 5/6 hypoxic (5%O2) cycles/h, 10.5 h/day during 28 and 35 daysincreased arterial blood pressure. Insulin resistance and insulinemia increased with CIH duration, beingsignificantly different after 35 days of CIH. Thirty-five days of CIH decreased insulin receptor expressionand phosphorylation in skeletal muscle and adipose tissue, but not in the liver. Conversely, Glut2 expres-sion increased in the liver of CIH-animals. Thirty-five days of CIH up-regulated HIF-1 in the liver anddown-regulated HIF-1 and HIF-2 in skeletal muscle.We concluded that the effect of CIH on insulin sensitivity and signaling is time-dependent and isassociated with changes in HIF signaling in insulin-sensitive tissues.
- Micro Computed Tomography Detects Changes in Liver Density in Control and in Prediabetes RatsPublication . Fonseca, A. R.; Franco, M. C.; Sacramento, J.; Melo, B.; Conde, S.V.; Guarino, M. P.Fatty liver disease is an early event in the development of insulin resistance that predicts the presence and progression of the metabolic syndrome. In humans, fatty liver diagnosis is usually performed by imaging techniques based on ultrasound, computed tomography and magnetic resonance. Rodent models are often used in metabolic research allowing access to tissue biopsies however, studies describing ex vivo computed tomography of biological samples are scarce. X-ray Micro Computed Tomography (Micro-CT) is an imaging technique that reveals the internal structure of materials in great detail, also allowing a quantitative analysis of properties such as density measured as arbitrary Hounsfield Units (HU). Herein, we tested the hypothesis that Micro CT detects changes in liver tomographic density induced by metabolic diseases and its reversal upon therapeutic surgical intervention. Two groups of male Wistar rats were used: a group submitted to a hypercaloric diet for 14 weeks to induce prediabetes and the control group submitted to a standard diet). The animals were randomly submitted to a surgical treatment and maintained on their respective diets after the procedure for 11 more weeks. Liver and adipose tissues samples were excised and samples were scanned using a compact X-ray micro-CT scanner. The projection images obtained were analyzed and reconstructed and values of HU density were calculated after calibration for all samples. Results showed that liver density was lower in prediabetes rats (74.8±5.87 HU) than in control animals (97.2±6.3 HU), p<0.05. Liver density was not affected by surgical treatment in control animals however, in prediabetes animals, the surgical therapy restored liver density to control values. Visceral fat density was significantly lower than hepatic density, as expected and was affected, neither by the disease condition nor by the surgical treatment. We concluded that micro-CT detects metabolic disease-induced changes in liver density, but not in visceral adipose tissue density in biopsy samples ex vivo. Changes in hepatic density, assessed by micro-CT, correlate with disease state and with therapeutic interventions.