According to the motivation, in Ruas’ work, “a meticulous molecular and physiological approach has allowed him to elucidate critical signalling pathways in skeletal muscle, liver and fat tissue. These include that of PGC1, and are critical for cellular and whole body metabolic control. His most recent work, published in some of the most prestigious journals in the world, has identified kynurenines, a class of molecules made from the amino acid tryptophan, as important signalling molecules in metabolism. The importance of kynurenines may not be restricted to type 2-diabetes but may also involve a plethora of other diseases in the gut, as well as in the central nervous and immune systems”.
Skeletal muscle represents almost 50 per cent of a person’s body weight, and it can adapt to many different challenges such as running and lifting weights, but also to diseases such as diabetes.
“What we are trying to understand is which molecules and mechanisms are involved in those adaptations, so we can use the positive adaptation that happens during exercise and try to apply it to a patient with diabetes. PGC-1 is one of those important molecules in muscle and in other tissues. In very general terms, PGC-1 regulates the capacity to generate and utilize the energy that cells and tissues need. This capacity is increased by exercise and reduced in diabetic muscle. Now that we know that PGC-1 is important in the regulation of these processes, we are trying to develop ways to increase and activate PGC-1 in muscle, something that could be a future antidiabetic therapy”, says Jorge Ruas.
Kynurenines are involved in many processes in the body, most notably brain function and psychiatric diseases.
“What we have found is that if you exercise you reduce the levels of the “bad” kynurenines in your brain, and you can reduce the incidence of diseases such as depression. This happens because muscles will remove kynurenine from circulation. We also found that kynurenines play important roles in regulating how tissues use energy - which of course is important in diabetes. Interestingly, the two aspects are very connected because diabetic patients have a higher incidence of co-morbidities such as depression when compared to other chronic diseases.”
Jorge Ruas will receive the Leif C Groop award and 100 000 SEK in conjunction with the Diabetes Research Day at Lund University at the Clinical Research Centre in Malmö on February 13th 2018. The Leif C. Groop award for outstanding diabetes research is sponsored by NovoNordisk Scandinavia and awarded annually to a young diabetes investigator.
Jorge Ruas, associate professor Karolinska Institute: www.ki.se/research/jorgeruas, Jorge [dot] Ruas [at] ki [dot] se, phone: +46 8 524 87261
Hindrik Mulder professor Lund University and head of the prize committee: hindrik [dot] mulder [at] med [dot] lu [dot] se, phone: +46-40-391023, +46-702-926 928