Metabolic disorders like obesity and Type 2 diabetes affect millions of individuals, contributing to significant morbidity and mortality worldwide being clear that the existing therapies are clearly scarce to address this problem. Our group is focused on the pathophysiology of metabolic diseases and the identification of prevention strategies and treatment interventions that would help stem this epidemic.
Our primary focus is the carotid body, a peripheral chemoreceptor, classically defined as a hypoxia sensor. We have recently discovered that the carotid body also senses hyperinsulinemia, and have shown that carotid body overactivation is present in hypercaloric animal models of type 2 diabetes and metabolic syndrome. We have also found that carotid sinus nerve (CSN) resection, the carotid body sensitive nerve, prevents and reverses insulin resistance, glucose intolerance, hypertension and obesity induced by hypercaloric diets, suggesting that the carotid body is involved in the genesis of metabolic disturbances. Additionally, more recently, we demonstrated for the 1st time that we are able to neuromodulate electrically the CSN to restore insulin sensitivity and glucose tolerance in type 2 diabetes rats. Aiming to facilitate the emergence of this therapeutic to address the unmet medical needs for type 2 diabetes, we are now mapping carotid body neural pathways, characterizing the CSN nerve fibers and disclosing the molecular mechanisms involved in the aetiology of insulin resistance and obesity.
Additionally, we have a second line of research that aims to investigate if the modulation of adenosine signaling or metabolism in insulin-sensitive tissues ameliorates glucose metabolism and tissue function in metabolic diseases. The mapping of neural pathways and the disclosure of the molecular mechanisms involved in type 2 diabetes and related co-morbidities should reveal new targets for therapeutic intervention.
Discover more about the Neuronal Control of Metabolic disturbances: Therapeutic Strategies Lab
- Diabetes: Peripheral nerve modulation to treat metabolic disease
- Acting on the potential of action potentials: will bioelectronic medicines be the next biologics?
- Técnica de modulação eletrónica permite controlar a diabetes tipo 2
- Electronic modulation of carotid sinus nerve can be used as a treatment for type 2 diabetes in rats
- Electronic modulation of carotid sinus nerve can be used as a treatment for type 2 diabetes in rats - Diabetologia
- Investigadores portugueses descobrem método que pode eliminar diabetes tipo 2
- Investigação em quatro frentes.
- Corpo carotídeo: a peça que faltava?
- Investigação da Faculdade de Ciências Médicas da Nova com prémio e na New Scientist
- Electric Medicine: Hack Body Electricity to Heal
- Diabetes: Eletricidade que cura
- Healing spark: Hack body electricity to replace drugs
- Maratona da Saúde
- Mundo Novo. Cafeína e a Diabetes
- Medalhas de Honra L'Oréal Portugal para as Mulheres na Ciência
Aug 2016 - Feb 2018 - “The Carotid Body as a therapeutic target in metabolic diseases: Mapping carotid sinus nerve activity in diabetes rat models: Lisbon Stage 2”. supported by: Galvani Biolectronics - 340.316,00€ - PI: Sílvia Conde
Nov 2013 - Apr 2016 - “The Carotid Body as a therapeutic target in metabolic diseases: Mapping carotid sinus nerve activity in diabetes rat models”. supported by: GSK Biolectronic Exploratory Funding - 147.905,56€ PI: Sílvia Conde
Mar 2015 - Apr 2016 - "Wireless Interfacing of the Carotid Sinus Nerve for Hypoxic Response Modulation". Colaboration project between CEDOC, NOVA Medical School, Universty of Texas and Illinois Institute of Technology. Supported by: GSK Innovation Challenge Funding. 200.000$ (total), 49.728$ (Silvia Conde). co-PIs: Mário Romero and Sílvia Conde
Mar 2014 - Feb 2015 – “Mapping the sympathetic efferent activity in carotid-body mediated insulin resistance”. Supported by: Portuguese Foundation for Science and Technology (EXPL/NEU-SCC/2183/2013) – 48.371€ PI: Maria Guarino
Nov 2013 - Nov 2014 - "Mapping carotid sinus nerve activity in diabetes rat models" Supported by: GSK Bioelectronic Exploratory Funding Ref: D00006317 - 96.105$ PI: Silvia Conde
Mar 2011 - Dec 2013 - "Insulin and carotid body: a new mechanism for insulin resistance and hypertension.".Supported by Portuguese Foundation for Science and Tecnhology Project Reference: PTDC/SAU-ORG/11149/2009 - 100.000€ PI: Silvia Conde
Nov 2009 - May 2012: Effect of chronic caffeine intake on insulin resistance and hypertension: mechanistic and therapeutic approach. Supported by: Sociedade Portuguesa Diabetologia/Lilly Portugal - 10.000 € PI: Silvia Conde and Maria Guarino
Prizes and Awards
2017: 1st Prize “De Castro-Heymans- Neil Award” by ISAC (International Society for Arterial Chemoreception) to the best work presented by a Young Research each triennial ISAC Meeting. (to Joana F. Sacramento )
2016 National Diabetes Award 2016 from the Portuguese Society of Diabetes
2016 Hargreaves 2016 Award from the Portuguese Society of Diabetes/JABA RECORDATI
2014 Best project in the Translational Research category by Fundação AstraZeneca Innovate Competition. (to Bernardete Melo)
2014 1st Prize “De Castro-Heymans- Neil Award” by ISAC (International Society for Arterial Chemoreception) to the best work presented by a Young Research each triennial ISAC Meeting. ( to Maria João Ribeiro)
2014 EPHAR Young Investigator Award from the Federation of European Pharmacological Societies to best scientific article published in the area of pharmacology. (to Maria João Ribeiro)
2012 Hargreaves 2012 Award from the Portuguese Society of Diabetes /JABA RECORDATI
2009 L’Oreal Portugal Medals of Honour for Women in Science from L’Oreal, Portuguese Science and Technology Foundation and UNESCO
2009 Nuno Castel Branco Award from the Portuguese Society of Diabetes and Lilly Portugal
2002 1st Prize “De Castro - Heymans – Neil Award” from the International Society for Arterial Chemoreception
2002 Pfizer Honour Young Researcher Prize from the Portuguese Society of Medical Sciences
1999 Training Fellowship - nº1/3.2/PRODEPIII/2000 from Fundo Social Europeu e Estado Português
- Conde SV, Chew DJ, Famm K, Guarino MP, Holinski B, Patel S (2015) Neuromodulation device. Patent PCT/PT2015/000047.
- Conde SV. Ablation of the carotid bodies in disease: meeting its adverse effects. J Physiol. 2018 Jan 31. doi: 10.1113/JP275796. [Epub ahead of print]
- Conde SV, Sacramento JF, Guarino MP. Carotid body: a metabolic sensor implicated in insulin resistance. Physiol Genomics. 2018 Jan 26. doi: 10.1152/physiolgenomics.00121.2017. [Epub ahead of print]
- Sacramento JF, Chew DJ, Melo BF, Donegá M, Dopson W, Guarino MP, Robinson A, Prieto-Lloret J, Patel S, Holinski BJ, Ramnarain N, Pikov V, Famm K, Conde SV. Bioelectronic modulation of carotid sinus nerve activity in the rat: a potential therapeutic approach for type 2 diabetes. Diabetologia. 2018 Jan 14. doi: 10.1007/s00125-017-4533-7. [Epub ahead of print]
- Sacramento JF, Chew DJ, Melo BF, Donegá M, Dopson W, Guarino MP, Robinson A, Prieto-Lloret J, Patel S, Holinski BJ, Ramnarain N, Pikov V, Famm K, Conde SV (2017). Bioelectronic modulation of carotid sinus nerve activity in the rat: a potential therapeutic approach for type 2 diabetes. Diabetologia (in press)
- Rodrigues T, Matafome P, Sereno J, Almeida J, Castelhano J, Gamas L, Neves C, Gonçalves S, Carvalho C, Arslanagic A, Wilcken E, Fonseca R, Simões I, Conde SV, Castelo-Branco M, Seiça R (2017) Methylglyoxal-induced glycation changes adipose tissue vascular architecture, flow and expansion, leading to insulin resistance. Sci Rep. 2017 May 10;7(1):1698. doi: 10.1038/s41598-017-01730-3.
- Sacramento JF, Ribeiro MJ, Rodrigues T, Olea E, Melo BF, Guarino MP, Fonseca-Pinto R, Ferreira CR, Coelho J, Obeso A, Seiça R, Matafome P, Conde SV. (2017) Functional abolition of carotid body activity restores insulin action and glucose homeostasis in rats: key roles for visceral adipose tissue and the liver. Diabetologia. Jan;60(1):158-168.
- Queiroga CS, Alves RM, Conde SV, Alves PM, Vieira HL. (2016) Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice. J Cell Sci. 129(16):3178-88. doi: 10.1242/jcs.187260.
- Conde SV, Ribeiro MJ, Melo BF, Guarino MP, Sacramento JF. (2016) Insulin resistance: a new consequence of altered carotid body chemoreflex? J Physiol. doi: 10.1113/JP271684. [Epub ahead of print]
- Sacramento JF, Ribeiro MJ, Rodrigues T, Guarino MP, Diogo LN, Seiça R, Monteiro EC, Matafome P, Conde SV. (2016) Insulin resistance is associated with tissue-specific regulation of HIF-1α and HIF-2α during mild chronic intermittent hypoxia. Respir Physiol Neurobiol. 228:30-8. doi: 10.1016/j.resp.2016.03.007.
- Quintero M, Olea E, Conde SV, Obeso A, Gallego-Martin T, Gonzalez C, Monserrat JM, Gómez-Niño A, Yubero S, Agapito T. (2016) Age protects from harmful effects produced by chronic intermittent hypoxia. J Physiol. 594(6):1773-90. doi: 10.1113/JP270878.
- Olea E, Ribeiro MJ, Gallego-Martin T, Yubero S, Rigual R, Masa JF, Obeso A, Conde SV, Gonzalez C. (2015) The carotid body does not mediate the acute ventilatory effects of leptin. Adv. Exp. Med. Biol. 860:379-85)
- Vera-Cruz P, Guerreiro F, Ribeiro MJ, Guarino MP, Conde SV. (2015) Hyperbaric oxygen therapy improves glucose homeostasis in type 2 diabetes patients: a likely involvement of the carotid bodies. Adv. Exp. Med. Biol. 860:221-5)
- Sacramento JF, Ribeiro MJ, , Yubero S, Melo BF, Obeso A, Guarino MP, Gonzalez C, Conde SV (2015) Disclosing caffeine action on insulin sensitivity: effects on rat skeletal muscle. 70.107:116
- Sacramento JF, Gonzalez C, Gonzaçez-Martin MC, Conde SV. (2015) Adenosine receptor blockade by caffeine inhibits carotid sinus nerve chemosensory activity in chronic intermittent hypoxic animals. Adv. Exp. Med. Biol. 860:133-7)
- Conde SV, Sacramento JF, Guarino MP, Gonzalez C, Obeso A, Diogo LN, Monteiro EC, Ribeiro MJ (2014) Carotid body, insulin, and metabolic diseases: unraveling the links. Front Physiol.5:418. doi: 10.3389/fphys.2014.00418. eCollection 2014. Review.
- Conde SV, Sacramento JF, Ribeiro MJ, Melo BF, Guarino MP. (2015) Insulin resistance: a new consequence of altered carotid body chemoreflex? Aut. Neu. 192(16)
- Gonzalez C, Conde SV, Gallego-Martin T, Olea E, Gonzalez-Obeso E, Ramirez M, Yubero S, Agapito MT, Gomez-Niño A, Obeso A, Rigual R, Rocher A (2014) Fernando De Castro and the discovery of the arterial chemoreceptors. Front. Neuroanat. 8:25 doi: 10.3389/fnana.2014.00025
- Conde SV and Peers C (2013) Carotid body chemotransduction gets the human touch. J Physiol 591:6131-2.
- Ribeiro MJ, Sacramento JF, Gonzalez C, Guarino MP, Monteiro EC, Conde SV (2013) Carotid body denervation prevents the development of insulin resistance and hypertension induced by hypercaloric diets. Diabetes 62:2905-16
- Guarino MP, Ribeiro MJ, Sacramento JF, Conde SV (2013) Chronic caffeine intake reverses age-induced insulin resistance in the rat: effect on skeletal muscle Glut4 transporters and AMPK activity. Age 35:1755-65
- Sacramento JF, Ribeiro MJ, Guarino MP, Conde SV (2013) Are the acute caffeine effects on insulin sensitivity mediated by adenosine receptors? Proceedings of the 6th European Congress of Pharmacology, 223-228
- Conde SV, Ribeiro MJ, Obeso A, Rigual R, Monteiro EC, Gonzalez C (2012) Chronic caffeine intake in adult rat inhibits carotid body sensitization produced by chronic sustained hypoxia but maintains intact chemoreflex output. Mol Pharmacol 2012 82:1056-65.
- Conde SV, Obeso A, Monteiro EC, Gonzalez C (2012) Effect of chronic caffeine intake on carotid body catecholamine dynamics in control and chronically hypoxic rats. Adv Exp Med Biol 758:315-23
- Conde SV, Monteiro EC, Rigual R, Obeso A, Gonzalez C (2012) Hypoxic intensity: a determinant for the contribution of ATP and adenosine to the genesis of carotid body chemosensory activity. J Appl Physiol. 112:2002-10.
- Conde SV, Nunes da Silva T, Gonzalez C, Mota Carmo M, Monteiro EC, Guarino MP. (2012) Chronic caffeine intake decreases circulating catecholamines and prevents diet-induced insulin resistance and hypertension in rats. Br J Nutr 107:86-95
- Gonzalez-Martín M.C., Vega-Agapito M.V, Conde S.V., Castañeda J. Bustamante R., Olea E., Perez-Vizcaino F., Gonzalez C. and Obeso A. (2011) Carotid body function and ventilatory responses in intermittent hypoxia. Evidence for anomalous brainstem integration of arterial chemoreceptor input. J Cell Physiol. 226:1961-9
- Gonzalez C., Agapito M.T., Rocher A., Gomez-Niño A., Rigual R., Castañeda J., Conde S.V. and Obeso A. (2010) A revisit to O(2) sensing and transduction in the carotid body chemoreceptors in the context of reactive oxygen species biology. Respir Physiol Neurobiol. Dec 174:317-30
- Conde S.V., Monteiro E.C., Obeso A. and Gonzalez C. (2009) Adenosine in peripheral chemoreception: new insights into a historically overlooked molecule. In: Arterial Chemoreceptors. (Gonzalez et al., eds), pp 159-174. Springer, Netherlands
- Conde S.V., Obeso A., Monteiro E.C. and Gonzalez C. (2009) The A2B-D2 receptor interaction that controls carotid body catecholamines release locates between the last two steps of hypoxic transduction cascade. In: Arterial Chemoreceptors. (Gonzalez et al., eds), pp 175-182. Springer, Netherlands
- Conde S.V., Gonzalez C., Batuca J.R., Monteiro E.C. and Obeso A. (2008) An antagonistic interaction between A2B adenosine and D2 dopamine receptors modulates the function of rat carotid body chemoreceptor cells. J Neurochem. 107, 1369-1381.
- Conde S.V., Obeso A. and Gonzalez C. (2007) Low glucose effects on rat carotid body chemoreceptor cells secretory responses and action potential frequency in the carotid sinus nerve. J. Physiol. 585, 721-730.
- Conde SV, Obeso A, Rigual R, Monteiro EC and Gonzalez C (2006) Function of the rat carotid body chemoreceptors in aging. J Neurochem. 99, 711-723.
- Conde S.V., Obeso A., Vicario I., Rigual R., Rocher A. and Gonzalez C. (2006), Caffeine inhibition of rat carotid body chemoreceptors is mediated by A2A and A2B adenosine receptors, J. Neurochem., 98, 616-628.
- Conde SV and Monteiro EC (2006) Activation of nicotinic ACh receptors with alpha 4 subunits induces adenosine release at the rat carotid body. Br J Pharmacol., 147, 783-789.
- Conde SV, Caceres AI, Vicario I, Rocher A, Obeso A and Gonzalez C.(2006) An overview on the homeostasis of Ca2+ in chemoreceptor cells of rabbit and rat carotid bodies. Adv. Exp. Med. Biol. 580, 215-222
- Conde SV and Monteiro EC (2006) Profiles for ATP and adenosine release at the carotid body in response to O2 concentrations. Adv. Exp. Med. Biol. 580, 179-184
- Conde SV and Monteiro EC (2004) Hypoxia induces adenosine release from the rat carotid body. J Neurochem, 89:1148-56.
- Conde SV and Monteiro EC (2003) Adenosine-acetylcholine interactions at the rat carotid body. Adv Exp Med Biol. 536:305-11.
- Galvani Bioelectronics, United Kingdom
- Maria P. Guarino - Leiria Polytechnic Institute, Leiria, Portugal
- Rui Fonseca-Pinto - Instituto de Telecomunicações and Politécnico de Leiria
- Paulo Matafome and Raquel Seiça - IBILI Coimbra
- Phillipe Blancou and Nicolas Glaichenhaus - INSERM, Université Nice, Nice, France
- Ana Obeso, Asuncion Rocher, Jesus Prieto-LLoret - Faculty of Medicine, University of Valladolid, Spain
- Silvestro Micera - Sant'Anna School of Advanced Studies, Pisa, Italy