Journal article
Dopamine regulates pancreatic glucagon and insulin secretion via adrenergic and dopaminergic receptors
TRANSLATIONAL PSYCHIATRY, v 11(1), 59
16 Feb 2021
PMID: 33589583
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Dopamine (DA) and norepinephrine (NE) are catecholamines primarily studied in the central nervous system that also act in the pancreas as peripheral regulators of metabolism. Pancreatic catecholamine signaling has also been increasingly implicated as a mechanism responsible for the metabolic disturbances produced by antipsychotic drugs (APDs). Critically, however, the mechanisms by which catecholamines modulate pancreatic hormone release are not completely understood. We show that human and mouse pancreatic alpha- and beta-cells express the catecholamine biosynthetic and signaling machinery, and that alpha-cells synthesize DA de novo. This locally-produced pancreatic DA signals via both alpha- and beta-cell adrenergic and dopaminergic receptors with different affinities to regulate glucagon and insulin release. Significantly, we show DA functions as a biased agonist at alpha(2A)-adrenergic receptors, preferentially signaling via the canonical G protein-mediated pathway. Our findings highlight the interplay between DA and NE signaling as a novel form of regulation to modulate pancreatic hormone release. Lastly, pharmacological blockade of DA D-2-like receptors in human islets with APDs significantly raises insulin and glucagon release. This offers a new mechanism where APDs act directly on islet alpha- and beta-cell targets to produce metabolic disturbances.
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Details
- Title
- Dopamine regulates pancreatic glucagon and insulin secretion via adrenergic and dopaminergic receptors
- Publication Details
- TRANSLATIONAL PSYCHIATRY, v 11(1), 59
- Publisher
- SPRINGERNATURE; LONDON
- Grant note
- We thank Drs. George Gittes, Yi Sheng, Andrea Workman, Kyle Orwig, Nicholas Pierre, and Julie Valleghe. These studies were supported by the Department of Defense (PR141292) (Z.F., D.A.), the John F. and Nancy A. Emmerling Fund of The Pittsburgh Foundation (Z.F.), NIH R21AG068607 (Z.F.), the Intramural Research Program of the National Institute of Neurological Disorders and Stroke (NINDS) in the National Institutes of Health (NIH) (M.S.-S., R.B.F., D.R.S.), Veterans Affairs VA-ORD-BLR&D I01BX002678 (V.K.Y.), and NIH R01DK097160 (V.K.Y.). Schematic figures were created with BioRender.com.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University
- Web of Science ID
- WOS:000618358500001
- Scopus ID
- 2-s2.0-85101472533
- Other Identifier
- 991021860761804721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Psychiatry