Antipsychotic drugs (APDs) are among the most widely prescribed medications. However, these drugs also cause profound metabolic disturbances including weight gain, glucose intolerance, and insulin resistance, and increase the risks of type 2 diabetes and cardiovascular disease. Significantly, all APDs cause metabolic side effects to differing degrees, and current treatments to reduce these metabolic symptoms have only limited efficacy. The single unifying property of all APDs is their blockade of dopamine D2-like receptors suggesting a role for these receptors in APD-induced metabolic dysfunction. Notably, we and others found that APDs not only act on dopamine receptors in the brain, but also act on the same receptors in the pancreas where they alter the release of hormones including insulin. These APD actions in the pancreas provide a critical new mechanism that may explain why antipsychotic drugs disrupt metabolic regulation and offer new treatment targets to improve these medications’ metabolic effects.

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