Anti-incretin, Anti-proliferative Action of Dopamine on β-Cells
| Autor: | Adolfo Garcia-Ocaña, Ann Marie Segal, Juan Carlos Alvarez-Perez, Paul L. Harris, Antonella Maffei |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Adult
Blood Glucose Male medicine.medical_specialty Dopamine medicine.medical_treatment Incretin Gastric Inhibitory Polypeptide Biology Cell Line Rats Sprague-Dawley Islets of Langerhans Endocrinology Gastric inhibitory polypeptide Glucagon-Like Peptide 1 Insulin-Secreting Cells Internal medicine Insulin Secretion Calcium flux medicine Animals Humans Insulin Autocrine signalling Molecular Biology Cell Proliferation Original Research Anti-incretin Anti-proliferative digestive oral and skin physiology General Medicine Middle Aged Glucagon-like peptide-1 Rats Signal transduction Somatostatin Homeostasis |
| Zdroj: | Molecular endocrinology (Baltim. Md.) 29 (2015): 542–547. doi:10.1210/me.2014-1273 info:cnr-pdr/source/autori:Maffei A, Segal AM, Alvarez-Perez JC, Garcia-Ocaña A, Harris PE./titolo:Anti-incretin, Anti-proliferative Action of Dopamine on ?-Cells./doi:10.1210%2Fme.2014-1273/rivista:Molecular endocrinology (Baltim. Md.)/anno:2015/pagina_da:542/pagina_a:547/intervallo_pagine:542–547/volume:29 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | Human islet ?-cells exploit an autocrine dopamine (DA)-mediated inhibitory circuit to regulate insulin secretion. ?-Cells also express the DA active transporter and the large neutral amino acid transporter heterodimer enabling them to import circulating DA or its biosynthetic precursor, L-3,4-dihydroxyphenylalanine (L-DOPA). The capacity to import DA or L-DOPA from the extracellular space possibly indicates that DA may be an endocrine signal as well. In humans, a mixed meal stimulus is accompanied by contemporary serum excursions of incretins, DA and L-DOPA, suggesting that DA may act as an anti-incretin as postulated by the foregut hypothesis proposed to explain the early effects of bariatric surgery on type 2 diabetes. In this report, we take a translational step backwards and characterize the kinetics of plasma DA and incretin production after a mixed meal challenge in a rat model and study the integration of incretin and DA signaling at the biochemical level in a rodent ?-cell line and islets. We found that there are similar excursions of incretins and DA in rats, as those reported in humans, after a mixed meal challenge and that DA counters incretin enhanced glucose-stimulated insulin secretion and intracellular signaling at multiple points from dampening calcium fluxes to inhibiting proliferation as well as apoptosis. Our data suggest that DA is an important regulator of insulin secretion and may represent 1 axis of a gut level circuit of glucose and ?-cell mass homeostasis. |
| Databáze: | OpenAIRE |
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