Striatal dopamine regulates systemic glucose metabolism in humans and mice

Kasper W Ter Horst, Nicolette M Lammers, Richard Trinko, Darren M Opland, Martijn Figee, Mariette T Ackermans, Jan Booij, Pepijn van den Munckhof, P Richard Schuurman, Eric Fliers, D. Denys, Ralph J DiLeone, Susanne E la Fleur, Mireille J Serlie

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

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.

Original languageEnglish
JournalScience Translational Medicine
Volume10
Issue number442
DOIs
Publication statusPublished - 2018

Keywords

  • Journal Article

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