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Anthony Raffo
Anthony Raffo
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Kolbe Hancock
Kolbe Hancock
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Teresa Polito
Teresa Polito
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Yuli Xie
Yuli Xie
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Gordon Andan
Gordon Andan
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Piotr Witkowski
Piotr Witkowski
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Mark Hardy
Mark Hardy
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Pasquale Barba
Pasquale Barba
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Caterina Ferrara
Caterina Ferrara
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Antonella Maffei
Antonella Maffei
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Matthew Freeby
Matthew Freeby
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Robin Goland
Robin Goland
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Rudolph L Leibel
Rudolph L Leibel
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Ian R Sweet
Ian R Sweet
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Paul E Harris
Paul E Harris
Department of Medicine, Barnard College, Department of Surgery of Columbia University Medical Center, Department of Surgery, Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, Naomi Berrie Diabetes Center, Department of Medicine, BB 20-06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
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Abstract
Despite different embryological origins, islet β-cells and neurons share the expression of many genes and display multiple functional similarities. One shared gene product, vesicular monoamine transporter type 2 (VMAT2, also known as SLC18A2), is highly expressed in human β-cells relative to other cells in the endocrine and exocrine pancreas. Recent reports suggest that the monoamine dopamine is an important paracrine and/or autocrine regulator of insulin release by β-cells. Given the important role of VMAT2 in the economy of monoamines such as dopamine, we investigated the possible role of VMAT2 in insulin secretion and glucose metabolism. Using a VMAT2-specific antagonist, tetrabenazine (TBZ), we studied glucose homeostasis, insulin secretion both in vivo and ex vivo in cultures of purified rodent islets. During intraperitoneal glucose tolerance tests, control rats showed increased serum insulin concentrations and smaller glucose excursions relative to controls after a single intravenous dose of TBZ. One hour following TBZ administration we observed a significant depletion of total pancreas dopamine. Correspondingly, exogenous l-3,4-dihydroxyphenylalanine reversed the effects of TBZ on glucose clearance in vivo. In in vitro studies of rat islets, a significantly enhanced glucose-dependent insulin secretion was observed in the presence of dihydrotetrabenazine, the active metabolite of TBZ. Together, these data suggest that VMAT2 regulates in vivo glucose homeostasis and insulin production, most likely via its role in vesicular transport and storage of monoamines in β-cells.
