Cel Hyperglycaemia in type 2 diabetes (T2D) doubles mortality and arises due to failure of pancreatic β-cell insulin secretory function to overcome insulin resistance. Exercise reduces hyperglycaemia by improving insulin sensitivity and β-cell function; however, the variability of this beneficial effect is huge and is associated with high blood glucose and poor insulin secretion. Hyperglycaemia increases interleukin-(IL)1β levels causing β-cell death and insulin secretory dysfunction (glucotoxicity), and these phenomena are all elevated in T2D and are also augmented by IL-6, which alone is not toxic to β-cells. Interestingly, blood IL-6 levels are not only increased in T2D but are also increased following exercise due to secretion from muscle. Therefore the huge variability in the adaptation to exercise may be due to muscle IL-6-induced enhancement of IL-1β-induced β-cell dysfunction. Thus, exercise may be detrimental to T2D patients with β-cell glucotoxicity. Our objective is to determine the independent and interactive roles of IL-6 and IL-1β in the adaptations to exercise in T2D. We will achieve this by integrating the human physiology expertise of the Experienced Researcher with the transgenic mouse model expertise of the Supervisor to create a bench-to-bedside approach from which both the host institution and the experienced researcher will gain from in the future. Innovative muscle-specific IL-6 knockout mouse models and clinical anti-IL-1β drug treatment approaches will be used to ultimately increase the knowledge of how IL-6 and IL-1β interact, making it possible to optimise exercise therapy for all T2D patients, including those who would otherwise be classified as a “non-responder”. Dziedzina nauki social sciencessociologydemographymortalitymedical and health sciencesbasic medicinephysiologypathophysiologymedical and health sciencesclinical medicineendocrinologydiabetes Program(-y) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Temat(-y) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Zaproszenie do składania wniosków H2020-MSCA-IF-2014 Zobacz inne projekty w ramach tego zaproszenia System finansowania MSCA-IF-EF-ST - Standard EF Koordynator THE UNIVERSITY OF BIRMINGHAM Wkład UE netto € 183 454,80 Adres Edgbaston B15 2TT Birmingham Zjednoczone Królestwo Zobacz na mapie Region West Midlands (England) West Midlands Birmingham Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 183 454,80
