Did you know dopamine has a role on both glucose uptake and Parkinson's Disease? This is one of the findings published in Frontiers in Pharmacology, by the Neuronal Control of Metabolic Disturbances group, led by researcher Sílvia Conde, at CEDOC-NMS. This research is first authored by Gabriela Tavares and constitutes an important step in the unveiling of these overlapping metabolic pathways.
What discoveries led you to the research described in your publication?
Dopamine is a key regulator of glucose metabolism in the central nervous system and is also present in the periphery where it may have direct effects on insulin-sensitive tissues. Bromocriptine, an agonist of one type of dopamine receptors, is an FDA-approved drug for type 2 diabetes. Previously, we showed that bromocriptine remodels dopamine signaling in adipose tissue and improves the metabolic profile in type 2 diabetes. Therefore, these findings suggest a possible peripheral action of bromocriptine, and consequently of dopamine, on glucose metabolism, which needs to be explored.
What were you trying to understand and what is the main discovery of this work?
We were trying to unravel the role of peripheral dopamine in the regulation of glucose uptake and metabolism in insulin-sensitive tissues. With this work we have, for the first time ,showed that peripheral dopamine stimulates glucose uptake with different roles for each of the dopamine receptors isoforms. We also showed for the first time that dopamine has a role in lipid metabolism in white adipose tissue.
Why is this important?
More studies were needed to clarify and test the hypothesis that dopamine, besides its important role in neuronal control, is also a peripheral modulator of insulin signaling and glucose uptake. Altogether, these results suggest that peripheral modulation of the dopaminergic system should be further evaluated as a putative therapeutic approach for metabolic disorders.
Can you use an analogy to help us understand your work?
Can you imagine that a molecule involved in an important neurological disorder like Parkinson can be also used to treat diabetes and/or obesity: this molecule is dopamine and besides its important role on transmitting the messages between the different parts of the brain and controlling the movement we have found to be also important to regulate the function of insulin in our fat.
What questions remain to be asked?
The formation of heterodimers between D2R and D1R are well established in the brain, however, there are no studies regarding this type of heterodimerization in the peripheral organs, which can confound the results found on this work about the different involvement of each dopamine receptor type on glucose metabolism in the periphery.
Also, dopamine is not able to cross the blood–brain barrier, so it remains to be addressed how indirect effects of dopamine over glucose metabolism conjugates with the peripheral direct effects that we showed here.
You can read the full article at Frontiers in Pharmacology, titled "Peripheral Dopamine Directly Acts on Insulin-Sensitive Tissues to Regulate Insulin Signaling and Metabolic Function", here.