Disclosing the caffeine dose to be administered that restores insulin sensitivity in prediabetes animal

Abstract

The results discussed in this thesis originated the following communications in International and National congresses: Sacramento JF, Coelho JC, Melo BF, Guarino MP and Conde SV. (2014) Assessment of caffeine dose and time of administration required for resetting insulin sensitivity in high sucrose diet in rats. 50th Meeting of EASD (European Association for the study of Diabetes), 14-19 September, Vienna, Austria Coelho JC, Melo BF, Sacramento JF, Guarino MP and Conde SV (2014). Establishing the caffeine dose that chronically restores insulin sensitivity in animal model of prediabetes. Fundação Astrazeneca Innovate Competition, iMed conference 6.0®, 10-12 October, Lisboa, Portugal Also, during the last year I was involved in other ongoing projects that originated the following communications: Coelho JC, Melo BF, Sacramento JF, Ribeiro MJ, Guarino MP and Conde SV (2014). Are the effects of carotid sinus nerve resection on insulin sensitivity mediated by an increase in Glut4 expression in skeletal muscle?. XLIV Reunião Anual da Sociedade Portuguesa de Farmacologia, XXXII Reunião de Farmacologia Clínica e XIII Reunião de Toxicologia, 5-7 February, Coimbra, Portugal Sacramento JF, Rodrigues T, Coelho JC, Matafome P, Ribeiro MJ, Seiça RM, Guarino MP, Conde SV (2014). Elucidating the mechanism by which carotid sinus nerve resection restores insulin sensitivity in pre-diabetes animal models. International Society for Arterial Chemoreception (ISAC) XIX University of Leeds, 29th June - 3rd July, Leeds, United KingdomType 2 diabetes mellitus (T2DM) is a chronic disease affecting millions of individuals, contributing to significant morbidity and mortality worldwide. Caffeine is the most widely consumed psychoactive substance in the world and recently several epidemiological studies described beneficial effects of chronic coffee intake on T2DM and metabolic syndrome. Our group has shown that chronic caffeine intake (1g/l) prevents the development of insulin resistance and hypertension in diet-induced insulin resistante rats. Therefore, the main objective of this work was to investigate the therapeutic dose of caffeine that restores insulin sensitivity in a prediabetic animal model. Experiments were performed in Wistar rats. The prediabetic animal model used was the high sucrose (HSu) model, which is obtained by submitting the animals to 35% of sucrose in drinking water during 28 days. The effect of chronic caffeine (0.5, 0.75 and 1g/l) was tested in control rats and in HSu model during 12 weeks assessing: insulin sensitivity, basal glycemia, glucose tolerance, adipose tissue mass, Glut4 transporters and nitric oxide (NO) content in skeletal muscle and in the liver. We have seen that chronic caffeine intake restores insulin sensitivity and glucose tolerance in HSu rats, being the latency time inversely correlated with caffeine concentration. Also, HSu diet did not change weight gain comparing with controls but increased fat mass. Caffeine intake did not alter weight gain/day and fat mass. Caffeine (1g/l) restores Glut4 expression levels in skeletal muscle in HSu animals. NO levels decrease in skeletal muscle in HSu animals, but not in the liver, and caffeine did not modify these levels. These results suggest that caffeine can be used as a therapeutical tool for the treatment of prediabetes and prevention of T2DM

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