Protein phosphorylation research unit
Protein phosphorylation is a biological process that regulates most aspects of cellular life, and the enzymes catalysing this reaction; protein kinases, constitute the largest family of enzymes encoded by the human genome.
An overall aim of our research is to study the regulation and function of protein phosphorylation cascades that are important for the maintenance of a normal energy metabolism and that might be involved in the pathophysiological changes in metabolism that ultimately lead to Type 2 Diabetes. We have a specific focus on protein kinases that regulate adipose tissue function, since defects in this tissue, for example in its ability to efficiently store fat, is an underlying cause of insulin resistance and diabetes.
We are currently investigating two protein kinases; AMP-activated protein kinase (AMPK) and Salt-inducible kinase 2 (SIK2), with the goal of determining their role in the control of adipocyte metabolism – both in healthy and in diseased states.
AMPK activation constitutes a strategy for the treatment of insulin resistance, because of the beneficial effects that this is predicted to have on glucose production in the liver and glucose uptake in muscle. The effect of AMPK activation in adipose tissue is however far less understood.
SIK2 is an AMPK-related kinase with abundant expression in adipose tissue and it has been shown in rodents that it regulates glucose- and lipid metabolism in adipocytes. We have found that SIK2 is markedly downregulated in human obesity and insulin resistance. Based on this, our goal is to determine if SIK2 directly affects insulin sensitivity – specifically in humans.
Our research will evaluate the usefulness of AMPK activation as an approach for treatment, by predicting the effect of AMPK activation in adipose tissue. The physiological relevance of our studies is reinforced by the use of human cells and tissue. Moreover, our work on SIK2 will address if downregulation of this protein is a causative factor in development of obesity and insulin resistance.
Examples of highlights of our research includes the following two publications, in which we investigated SIK isoforms in the liver and in adipocytes, respectively, and a press-release highlighting the latter:
- ”The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver.” Nature communications 2014;5:4535
- ”SIK2 regulates CRTCs, HDAC4 and glucose uptake in adipocytes.” J Cell Sci 2015;128:472-486
Another example of how we convey information about our work to the wider public is given in this recording of a talk during ”Forskningens Dag 2015”, which was broadcasted by Swedish National TV;