TY - JOUR
T1 - Striatal dopamine regulates systemic glucose metabolism in humans and mice
AU - ter Horst, Kasper W.
AU - Lammers, Nicolette M.
AU - Trinko, Richard
AU - Opland, Darren M.
AU - Figee, Martijn
AU - Ackermans, Mariette T.
AU - Booij, Jan
AU - Munckhof, Pepijn van den
AU - Schuurman, P. Richard
AU - Fliers, Eric
AU - Denys, Damiaan
AU - DiLeone, Ralph J.
AU - la Fleur, Susanne E.
AU - Serlie, Mireille J.
PY - 2018
Y1 - 2018
N2 - The brain is emerging as an important regulator of systemic glucose metabolism. Accumulating data from animal and observational human studies suggest that striatal dopamine signaling plays a role in glucose regulation, but direct evidence in humans is currently lacking. We present a series of experiments supporting the regulation of peripheral glucose metabolism by striatal dopamine signaling. First, we present the case of a diabetes patient who displayed strongly reduced insulin requirements after treatment with bilateral deep brain stimulation (DBS) targeting the anterior limb of the internal capsule. Next, we show that DBS in this striatal area, which induced dopamine release, increased hepatic and peripheral insulin sensitivity in 14 nondiabetic patients with obsessive-compulsive disorder. Conversely, systemic dopamine depletion reduced peripheral insulin sensitivity in healthy subjects. Supporting these human data, we demonstrate that optogenetic activation of dopamine D1 receptor–expressing neurons in the nucleus accumbens increased glucose tolerance and insulin sensitivity in mice. Together, these findings support the hypothesis that striatal neuronal activity regulates systemic glucose metabolism.
AB - The brain is emerging as an important regulator of systemic glucose metabolism. Accumulating data from animal and observational human studies suggest that striatal dopamine signaling plays a role in glucose regulation, but direct evidence in humans is currently lacking. We present a series of experiments supporting the regulation of peripheral glucose metabolism by striatal dopamine signaling. First, we present the case of a diabetes patient who displayed strongly reduced insulin requirements after treatment with bilateral deep brain stimulation (DBS) targeting the anterior limb of the internal capsule. Next, we show that DBS in this striatal area, which induced dopamine release, increased hepatic and peripheral insulin sensitivity in 14 nondiabetic patients with obsessive-compulsive disorder. Conversely, systemic dopamine depletion reduced peripheral insulin sensitivity in healthy subjects. Supporting these human data, we demonstrate that optogenetic activation of dopamine D1 receptor–expressing neurons in the nucleus accumbens increased glucose tolerance and insulin sensitivity in mice. Together, these findings support the hypothesis that striatal neuronal activity regulates systemic glucose metabolism.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85047564846&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29794060
U2 - https://doi.org/10.1126/scitranslmed.aar3752
DO - https://doi.org/10.1126/scitranslmed.aar3752
M3 - Article
C2 - 29794060
SN - 1946-6234
VL - 10
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 442
M1 - eaar3752
ER -