The rapid rise in obesity and associated spread of type 2 diabetes represent an enormous challenge for society, with no efficient and safe medicines to prevent or stop this development available. The failure to develop adequate treatments is thought to be due to the fact that the molecular machinery controlling systemic metabolism remains unknown. Now, a study from researchers at the Technical University of Munich shows that the human brain actively takes sugar from the blood. The team state that their findings suggest transportation of sugar into the brain is regulated by glia cells that react to hormones such as insulin or leptin; previously it was thought that this was only possible for neurons. The opensource study is published in the journal Cell.
Previous studies show that astrocytes are the most common cells in the brain. One of their jobs is to form the blood-brain barrier by enclosing the blood vessels that run in the brain, whilst selectively allowing certain substances through to the nerve cells. Recent studies have shown that astrocytes react to leptin, a metabolic hormone, which is an important factor for satiety. As both leptin and insulin have been shown to influence astrocytes, the lab proposed a new model which, in addition to the neurons, also takes astrocytes into account as adjustors of metabolism and the feeling of hunger. The current study investigates the possibility that insulin signalling in astrocytes plays a functional role in systemic metabolism.
The current study first examined the activity of insulin receptors on the surface of astrocytes, molecular structures which respond to insulin to influence cell metabolism. Results show that if this receptor was missing on certain astrocytes the result was less activity in proopiomelanocortin neurons, which curb food uptake. Data findings show that, at the same time, adaption of metabolism to challenges like sugar intake become impaired.
With the help of advanced imaging technologies such as positron emission tomography, the group were able to show that hormones such as insulin and leptin act specifically on support glia cells to regulate sugar intake into the brain, like a ‘sugar switch’. Results show that without insulin receptors, astrocytes became less efficient in transporting glucose into the brain, particularly in the satiety brain centres, which are located in the hypothalamus.
The team surmise that their data shows, for the first time, that essential metabolic and behavioural processes are not regulated via neuronal cells alone and that other cell types in the brain, such as astrocytes, play a crucial role. They go on to add that this represents a paradigm shift which could help explain why it has been so difficult to find medicines for diabetes and obesity until now. For the future, the researchers state that new studies will be necessary to adjust the old neural control of food intake model, where astrocytes also play a crucial role. They conclude that once there is a better understanding of this concept, the idea is to find ways and substances to modulate pathways for multiple cell types to curb sugar addiction.