Chronicles

What we normally call “sugar” is a substance called sucrose, composed of 1 molecule of fructose and 1 molecule of glucose. Food molecules such as glucose present in sugar, but also pasta, bread or legumes are very important sources of fuel. Glucose is broken down in a process that releases energy to be used by all our cells to function, from the muscle that contracts and allows us to move, to the brain neuron that fires and allows us to think.

Because the central nervous system is particularly dependent on glucose as fuel, glucose levels in blood need to be maintained as constant as possible. After a meal, blood glucose levels rise, a change that is detected by the pancreas - a glandular organ located behind the stomach. The so-called beta-cells of the pancreas are stimulated by this increase in glucose levels to secrete the hormone insulin into the bloodstream. Food provides an immense amount of glucose that can potentially increase blood glucose concentrations to harmful levels. The function of insulin is to signal the cells of the liver, the muscle and the adipose or fat tissues to take up glucose from the blood, thereby preventing the elevation of blood glucose levels.

Glucose that enters the cells will be used for energy production or stored as glycogen, an energy reservoir of muscle and liver cells. Once the glucose is taken up, blood glucose levels decrease and insulin is no longer secreted. In the first few hours after the meal, blood glucose levels fall below a certain point. In response, another hormone called glucagon is released. Glucagon restores normal glucose levels by converting the glycogen reservoirs of the liver back into glucose, which is released into the blood and by stimulating the synthesis of glucose from lactic acid and certain amino acids. This system ensures that blood glucose levels remain remarkably constant.

However, when insulin actions are impaired – a phenomenon called insulin resistance – post-meal glucose is not efficiently cleared and its blood levels increase. Importantly, this does not cause any discernible symptoms, hence it can silently prevail for years or even decades.  Eventually, this can lead to serious damage to the heart, blood vessels, eyes, kidneys and nerves. Why do cells become insulin resistant? As noted in a previous chronicle, our society has suffered a nutrient transition in which home-cooked meals have been largely replaced by hypercaloric pre-cooked or fast-food meals.

This has led us to consume more sugar, fats and salt that our body requires. At the same time, the reduction of physical demands at most work places, has dramatically reduced the amount of daily physical activity. As a consequence, there is an accumulation of fat that infiltrates the liver, pancreas and muscle, which causes these tissues to become resistant to the actions of insulin. As insulin resistance develops, the pancreas produces larger amounts of insulin in an attempt to maintain normal blood glucose levels. The additional burden that the increased insulin demands pose on the liver, may eventually impair and even kill the pancreatic cells leading to a collapse in insulin production and development of Type 2 Diabetes (T2DM).

This condition is characterized by chronically high levels of blood glucose. According to the International Diabetes Federation, about 425 million people worldwide suffer from diabetes and about 60 million people are affected by this disease in Europe. Perhaps more worrying, is that the number of deaths from diabetes represent 13% of all causes of global mortality. T2DM accounts for 90% of the cases of diabetes and is associated with several co-morbidities, such as hypertension, dyslipidemia or high levels if fat in the blood, and non-alcoholic fatty liver disease (NAFLD), which may be present even before the diagnosis of T2DM. All these diseases involve insulin resistance. In the case of the liver, this leads to the accumulation of fat inside the hepatic cells. Patients with NAFLD carry an increased risk of T2DM and patients with T2DM have a higher prevalence of NAFLD compared to subjects without diabetes.

Both T2DM and NAFLD are also major risk factors for the development of cardiovascular diseases, the major cause of death around the world. In fact, cardiovascular diseases are the most common cause of death in diabetic individuals, with the mortality rate reaching 80% in T2DM adult populations. But how can exercise help beat insulin resistance? T2DM is caused by over-nutrition and physical inactivity. It can be then expected that exercising might reverse insulin resistance and sensitize the cells of the different organs to the effects of insulin again. Indeed, exercise is part of the treatment strategy for T2DM and associated metabolic conditions.

These treatments aim to reduce the amount of fat accumulated in the body. Since muscle derives most of its energy from fat oxidation, increased muscle activity is effective at depleting excess fat and restoring insulin actions. Regular exercise practice, preferably in combination with a healthy diet, is important not just for the treatment but also the prevention of T2DM and associated metabolic diseases. So make sure you keep your cells responsive to insulin, eat well and keep it moving!

Authors: Sara Guerra, Inês Mateus and Bárbara Patrício are early stage researchers of the FOIE GRAS project. Sara Guerra is doing her research at the Consiglio Nazionale delle Ricerche (CNR), in Pisa (Italy) and at the Institut national de la Santé et de la Recherche Médicale (INSERM), in Paris (France). Inês Mateus is doing her research at the INSERM, at the Helmholtz Zentrum Muenchen Deutsches Forschungszentrum Fuer Gesundheit Und Umwelt GMBH (HMUG), in Muenchen (Germany), and at the Center for Neuroscience and Cell Biology (CNC), at the University of Coimbra (UC), in Coimbra (Portugal). Bárbara Patrício is doing her research at the CNR in Pisa (Italy), at the Associação Protetora dos Diabéticos de Portugal (APDP), in Lisbon (Portugal), at the CNC-UC in Coimbra (Portugal), and at the company Mediagnost (Germany).

The project: This chronicle results from the collaboration between the Center for Neuroscience and Cell Biology (CNC) of the University of Coimbra, the European Training Network FOIE GRAS (http://www.projectfoiegras.eu), the Erasmus+ Program and the Academic Sports Federation University (FADU) in the scope of the European University Games Coimbra 2018.

Coordination: Anabela Marisa Azul, João Ramalho-Santos, Mireia Alemany i Pagès, Paulo Oliveira and Sara Varela Amaral

Revision of the text: Mireia Alemany i Pagès, Anabela Marisa Azul, John Jones, João Ramalho-Santos, Amalia Gastaldelli, Carina Prip-Buus, Hans Zischka, Paula Macedo, Andrea Normann and Paulo Jorge Oliveira

Illustration: Rui Tavares

This chronicle reflects only the authors’ views and the Commission is not responsible for any use that may be made of the information it contains.