Dopamine-Mediated Autocrine Inhibitory Circuit Regulating Human Insulin Secretion in Vitro

作者：Simpson Norman; Maffei Antonella; Freeby Matthew; Burroughs Steven; Freyberg Zachary; Javitch Jonathan; Leibel Rudolph L; Harris Paul E^*

来源：Molecular Endocrinology, 2012, 26(10): 1757-1772.

DOI：10.1210/me.2012-1101

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 beta-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 beta-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. (Molecular Endocrinology 26: 1757-1772, 2012)

• 出版日期2012-10