It has long been recognised that behaviours controlled by the brain, such as overeating resulting in obesity, can contribute to diabetes risk. There is also growing recognition that the brain can play a role in the acute regulation of blood glucose in rodent models. Recently, technology has been developed that allow selective and rapid activation or inhibition of discrete neuronal populations; this is achieved by the use of Designer Receptors Exclusively Activated by Designer Drugs (DREADDS) and several similar variants. We sought to determine how the central melanocortin system rapidly regulated glucose levels by evaluating glucose tolerance and glucose uptake using 18Fluoro deoxy Glucose Positron Emission Tomography (18FdG PET) in mice that had acute activation or inhibition of melanocortin neuron activity.
We found that depolarizing Proopiomelanocortin (POMC) neurons increased glucose disposal into brown adipose tissue (BAT), and conversely activating Agouti related peptide (AgRP) neurons inhibited glucose uptake in BAT. These changes in BAT glucose uptake coincided with decreased and increased blood glucose levels respectively.
We propose that factors which act on melanocortin neurons might also acutely regulate blood glucose levels.