Cellular adaptations to training in patients with type 2 diabetes
Studying the effect of training on the microvascular cellular function in men and women (40-60 years) with and without type 2 diabetes.
The aim of this project is to study the skeletal muscle-derived microvascular cellular adaptations; and the transcriptional differences at single cell resolution in skeletal muscle and adipose tissue before and after a 12-week training intervention in patients with type 2 diabetes and in control subjects.
This will be done using a unique combination of clinical experiments and state-of-the-art cellular models (single nuclei transcriptomics and microvascular cellular isolations).
Physical training can improve metabolic health in patients with insulin resistance and/or type 2 diabetes (NIH, 2020). The cellular and molecular changes underlying these improvements are multifactorial and only partly understood. This adaptation is most likely at the multi-organ level to induce improvements in skeletal muscle glucose uptake and adipose tissue insulin sensitivity.
There are vast amounts of literature on the effects of an acute bout of exercise on glucose uptake in skeletal muscle (Sylow et al., 2017; Richter et al., 1989; Wojtaszewski et al., 2002; Frosig & Richter, 2009). However, there is a lack of data on the molecular basis for the insulin sensitizing effect of regular physical training, and in particular how the cellular adaptations to training may be changed in patients with type 2 diabetes.
Knowledge on the molecular and cellular changes in the improvements in human adipose tissue insulin sensitivity in response to regular training is even less explored.
A detailed map of the skeletal muscle-derived microvascular cells and adipose tissue insulin resistance, at baseline and in response to training, would substantially add to the wealth of knowledge in the field and would allow opportunities to identify novel therapeutic targets for treating insulin resistance.
This project is in collaboration with Novo Nordisk A/S and Faculty of Medical and Health Sciences, UCPH (SUND).