Modulation of carotid body activity as a therapeutic intervention in metabolic diseases.

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Publications

Carotid body chemosensitivity: Early biomarker of dysmetabolism in humans

Publication . Cunha-Guimaraes, João P; Guarino, Maria Pedro; Timóteo, Ana T; Caires, Iolanda; Sacramento, Joana F; Ribeiro, Maria J; Selas, Mafalda; Santiago, João C P; Mota-Carmo, Miguel; Conde, Silvia V

2020-06Journal article

Open access

Insulin resistance is associated with tissue-specific regulation of HIF-1α and HIF-2α during mild chronic intermittent hypoxia

Publication . 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.

2016-07Journal article

Restricted access

Evaluating the Impact of Different Hypercaloric Diets on Weight Gain, Insulin Resistance, Glucose Intolerance, and its Comorbidities in Rats

Publication . Melo, Bernardete F.; Sacramento, Joana F.; Ribeiro, Maria J.; Prego, Claudia S.; Correia, Miguel C.; Coelho, Joana C.; Cunha-Guimaraes, Joao P.; Rodrigues, Tiago; Martins, Ines B.; Seiça, Raquel M.; Matafome, Paulo; Conde, Silvia V.; Guarino, Maria Pedro

Animal experimentation has a long history in the study of metabolic syndrome-related disorders. However, no consensus exists on the best models to study these syndromes. Knowing that different diets can precipitate different metabolic disease phenotypes, herein we characterized several hypercaloric rat models of obesity and type 2 diabetes, comparing each with a genetic model, with the aim of identifying the most appropriate model of metabolic disease. The effect of hypercaloric diets (high fat (HF), high sucrose (HSu), high fat plus high sucrose (HFHSu) and high fat plus streptozotocin (HF+STZ) during different exposure times (HF 3 weeks, HF 19 weeks, HSu 4 weeks, HSu 16 weeks, HFHSu 25 weeks, HF3 weeks + STZ) were compared with the Zucker fatty rat. Each model was evaluated for weight gain, fat mass, fasting plasma glucose, insulin and C-peptide, insulin sensitivity, glucose tolerance, lipid profile and liver lipid deposition, blood pressure, and autonomic nervous system function. All animal models presented with insulin resistance and dyslipidemia except the HF+STZ and HSu 4 weeks, which argues against the use of these models as metabolic syndrome models. Of the remaining animal models, a higher weight gain was exhibited by the Zucker fatty rat and wild type rats submitted to a HF diet for 19 weeks. We conclude that the latter model presents a phenotype most consistent with that observed in humans with metabolic disease, exhibiting the majority of the phenotypic features and comorbidities associated with type 2 diabetes in humans.

2019-05-28Journal article

Open access