Muscle insulin resistance: a journey from lipid to glucose metabolism

Insulin is a hormone secreted by the pancreas after the ingestion of a meal rich in carbohydrates/sugars. This hormone stimulates different organs to capture the abundant glucose from the blood coming from the ingested meal. The skeletal muscle (muscle groups responsible for voluntary movement) is an important regulator of blood glucose levels, given that it stores a large fraction of this circulating glucose. High concentrations of fat in the blood interfere with this process, which may lead to what is called insulin resistance (IR). If the muscle becomes insulin-resistant, the pancreas needs to make more insulin to maintain normal glucose levels. Long-term, if the pancreas fails to sustain this high insulin production, this may culminate in the development of type 2 diabetes, a disease that affects more than 4% of the global adult population. 

In the muscle, fats can also be broken down to be used as an important energy source to promote contractions and movement. In this PhD thesis, I investigated how the breakdown of fats is involved in muscle IR. Many factors are known to influence both the breakdown of fats, as well as IR development. On the one hand, ageing and diets rich in fat are considered risk factors for IR. On the other hand, physical exercise has been shown to prevent IR, meaning that it makes the muscle more sensitive to the action of insulin. I studied the connection between fats and glucose in the context of ageing, exercise and diet. Exploring biological mechanisms that are involved in IR development and prevention is crucial to better understand and consequently treat IR. To answer the proposed scientific questions, I used a combination of experiments in mice, lab-cultured cells and computer simulations and developed new research tools.

Dissertation: http://hdl.handle.net/11370/380cd066-f330-4970-8b56-9469d604da33