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Dopamine-mediated autocrine inhibitory circuit regulating human insulin secretion in vitro.

ABSTRACT: We describe a negative feedback autocrine regulatory circuit for glucose-stimulated insulin secretion in purified human islets in vitro. Using chronoamperometry and in vitro glucose-stimulated insulin secretion measurements, evidence is provided that dopamine (DA), which is loaded into insulin-containing secretory granules by vesicular monoamine transporter type 2 in human ?-cells, is released in response to glucose stimulation. DA then acts as a negative regulator of insulin secretion via its action on D2R, which are also expressed on ?-cells. We found that antagonism of receptors participating in islet DA signaling generally drive increased glucose-stimulated insulin secretion. These in vitro observations may represent correlates of the in vivo metabolic changes associated with the use of atypical antipsychotics, such as increased adiposity.

SUBMITTER: Simpson N

PROVIDER: S-EPMC3458225 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Dopamine-mediated autocrine inhibitory circuit regulating human insulin secretion in vitro.

Simpson Norman N Maffei Antonella A Freeby Matthew M Burroughs Steven S Freyberg Zachary Z Javitch Jonathan J Leibel Rudolph L RL Harris Paul E PE

Molecular endocrinology (Baltimore, Md.) 20120821 10

We describe a negative feedback autocrine regulatory circuit for glucose-stimulated insulin secretion in purified human islets in vitro. Using chronoamperometry and in vitro glucose-stimulated insulin secretion measurements, evidence is provided that dopamine (DA), which is loaded into insulin-containing secretory granules by vesicular monoamine transporter type 2 in human β-cells, is released in response to glucose stimulation. DA then acts as a negative regulator of insulin secretion via its a ...[more]

PMID: 22915827

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