Our interest is to understand the pathophysiology of prediabetes, type 2 diabetes (T2D) and their comorbidities, and to effectively translate that knowledge into a better diagnosis and treatment of these multi-systemic disorders.
To better understand the pathophysiological mechanisms behind these metabolic diseases, we use an integrative approach looking at classical target tissues for insulin action: liver, muscle, and fat, as well as to other targets (e.g., brain).
In a truly translational approach, we use a wide range of genetic and biochemical approaches both in vitro, ex vivo, in vivo, including studies with human subjects. These studies are expected to lead to the development of novel biomarkers and therapeutic interventions in (pre)diabetes, non-alcoholic fatty liver disease (NAFLD) and to the improvement of health and wellbeing.To dissect the dynamics of (pre)diabetes and comorbidities, our lab is currently conducting several related and highly integrated projects, for which detailed information is provided below.
Team Members:Inês Coelho, Rita Machado de Oliveira, Akiko Teshima, Pedro Ribeiro, Pedro Pereira, Paula Macedo
Objective:We hypothesize that gut-derived exosomes (GDE) can act as mediators of gut-liver communication in T2D and NAFLD pathogenesis and progression. Importantly, blood exosomes cargo and unique surface markers will reflect the metabolic state of multiple organs, thus they hold the potential to be used as a minimally invasive diagnostics tool.Our ultimate goal is to identify novel biomarkers for T2D and NAFLD stratification towards patient-centered care and precision medicine approaches.Publications: Ferreira I, Machado de Oliveira R, Carvalho AS, Teshima A, Beck HC, Matthiesen R, Costa-Silva B, Macedo MP. Messages From the Small Intestine Carried by Extracellular Vesicles in Prediabetes: a Proteomic Portrait. bioRxiv 2021.02.19.431856; DOI:10.1101/2021.02.19.431856Acknowledgments:SPD; FCT (PTDC/MEC-MET/29314/2017); Programa Gilead Génese
Borges DO, Patarrão RS, Ribeiro RT, Machado de Oliveira R, Duarte N, Belew GD, Martins M, Andrade R, Costa J, Correia I, Boavida JM, Duarte R, Gardete-Correia L, Medina JL, Raposo JF, Jones JG, Penha-Gonçalves C, Macedo MP. Loss of postprandial insulin clearance control by Insulin-Degrading Enzyme drives dysmetabolism traits. Metabolism. 2021;118:154735. doi: 10.1016/j.metabol.2021.154735.
Coelho I, Duarte N, Barros A, Macedo MP, Penha-Gonçalves C. Trem-2 Promotes Emergence of Restorative Macrophages and Endothelial Cells During Recovery From Hepatic Tissue Damage. Front Immunol. 2021 11:616044. doi: 10.3389/fimmu.2020.616044.
Pina AF, Patarrão RS, Ribeiro RT, Penha-Gonçalves C, Raposo, JF, Gardete-Correia L, Duarte R, Boavida JM, Medina JL, Henriques R, Macedo MP. Metabolic Footprint, towards Understanding Type 2 Diabetes beyond Glycemia. Journal of Clinical Medicine 2020, 9(8):2588.
Pina A, Helgadottir S, Mancina RM, ..., Macedo MP, Valenti L, Volpe G, Romeo S. Virtual genetic diagnosis for familial hypercholesterolemia powered by machine learning. European Journal of Preventive Cardiology 2020:2047487319898951. doi: 10.1177/2047487319898951.
Bergman M, Abdul-Ghani M, DeFronzo RA, Manco M, Sesti G, Fiorentino TV, Ceriello A, Rhee M, Phillips LS, Chung S, Cravalho C, Jagannathan R, Monnier L, Colette C, Owens D, Bianchi C, Del Prato S, Monteiro MP, Neves JS, Medina JL, Macedo MP, Ribeiro RT, Raposo JF, Dorcely B, Ibrahim N, Buysschaert M. Review of methods for detecting glycemic disorders. Diabetes Research and Clinical Practice 2020, 165:108233
Borges DO, Meneses MJ, Dias TR, Martins FO, Oliveira PF, Alves MG, Macedo MP. Data on metabolic profile of insulin-degrading enzyme knockout mice. Data Brief. 2019;25:104023. doi:10.1016/j.dib.2019.104023.
Meneses MJ, Silvestre R, Sousa-Lima I, Macedo MP. Paraoxonase-1 as a Regulator of Glucose and Lipid Homeostasis: Impact on the Onset and Progression of Metabolic Disorders. Int J Mol Sci. 2019;20(16):4049. doi: 10.3390/ijms20164049.
Martins F, Delgado T, Viegas J, Gaspar J, O'Doherty R, Scott D, Macedo MP*; Jones J*. Mechanisms by which Thiazolidinediones Protect Against Sucrose-induced Fatty liver and Hyperinsulinemia Br J Pharmacol. 2016 Jan;173(2):267-78.
Natali A, Ribeiro R, Baldi S, Tulipani A, Rossi M, Venturi E, Mari A, Macedo MP, Ferrannini E. Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion. Diabetologia. 2013 May;56(5):1183-91. doi: 10.1007/s00125-013-2836-x
Duarte N, Coelho I, Holovanchuk D, Inês Almeida J, Penha-Gonçalves C, Macedo MP. Dipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells. Hepatol Commun. 2018 Sep 7;2(9):1080-1094.
João Silva, …, Maria Paula Macedo*, John G. Jones*. Determining Contributions of Exogenous Glucose and Fructose to de novo Fatty Acid and Glycerol Synthesis in Liver and Adipose Tissue. Metabolic Engineering (2019).
Huang H,…, Macedo MP, White M, Jones J, Kim YB. Rho-kinase/AMPK axis regulates hepatic lipogenesis during overnutrition. J Clin Invest. 2018;128(12):5335-5350.
Afonso RA, Gaspar JM, Lamarão I, Lautt WW, Macedo MP. Postprandial insulin action relies on meal composition and hepatic parasympathetics: dependency on glucose and amino acids. J Nutr Biochem. 2016;27:70-8.
Patarrão RS, Lautt WW, Afonso RA, Ribeiro RT, Fernandes AB, Boavida JM, Macedo MP. Postprandial but not fasting insulin resistance is an early identifier of dysmetabolism in overweight subjects. Can J Physiol Pharmacol. 2012;90(7):923-31. doi: 10.1139/y2012-086.
Fernandes AB, Guarino MP, Macedo MP. Understanding the in-vivo relevance of S-nitrosothiols in insulin action. Can J Physiol Pharmacol. 2012;90(7):887-94. doi: 10.1139/y2012-090.
The big winner of the 14th Edition of the Santander Collaborative Research Award/NOVA 2021 is the project “Graphene Smart Bandages for Diabetic Foot Ulcer Monitoring”. The responsible multidisciplinary team is made up of the researcher Inês Coelho, from group MEDIR at CEDOC and by the researcher João Coelho, from CENIMAT/I3N, from the NOVA School of Science and Technology | NEW FCT.
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