AMPK and SIK2 Signaling Networks in Adipose Tissue – Implications for Insulin Action and Resistance

The inability of adipocytes to properly respond to insulin, store lipids and produce lipokines, is a cause for systemic insulin resistance and type 2 diabetes (T2D). Our goal is to increase the understanding of why adipocytes become insulin resistant, by exploring the energy sensor and anti-diabetic drug target AMP-activated protein kinase (AMPK) and the related salt-inducible kinase (SIK) 2. We discovered that SIK2 is reduced in obesity and insulin resistance and required to maintain insulin sensitivity in adipocytes. Our work using novel AMPK activators challenge the former view of AMPK in adipocytes and indicate a role for this kinase in the regulation of fatty acid (FA) synthesis by insulin – a process disturbed in T2D.

Aims
Is AMPK dysregulated in insulin resistant states?
What is the role of AMPK in FA and lipokine synthesis, and its regulation by insulin?
By which mechanisms does SIK2 maintain insulin signaling and glucose uptake?
How does reduced SIK2 affect insulin-induced anti-lipolysis?
Which genes and novel pathways are controlled by SIK2?

We will use multiple methods to modulate AMPK and SIK2 and then monitor FA synthesis, lipokines, glucose uptake, anti-lipolysis and genes and proteins of interest. We have a strong collaborative network and are members of Lund University Diabetes Centre.

Our research is important since it will increase the understanding of how insulin resistance develops and if AMPK and SIK2 are useful targets for much needed treatments.