Abstract
The local synthesis of dopamine and its effects on insulin release have been described in isolated islets. Thus, it may be accepted that dopamine exerts an auto-paracrine regulation of insulin secretion from pancreatic beta cells. The aim of the present study is to analyze whether dopamine is a regulator of the proliferation and apoptosis of rat pancreatic beta cells after glucose-stimulated insulin secretion. Glucose stimulated pancreatic islets obtained from male Wistar rats were cultured with 1 or 10 μM dopamine from 1 to 12 h. Insulin secretion was analyzed by RIA. The cellular proliferation rate of pancreatic islets and beta cells was studied with immunocytochemical double labelling for both insulin and PCNA (proliferating cell nuclear antigen), and active caspase-3 was detected to evaluate apoptosis. The secretion of insulin from isolated islets was significantly inhibited (p<0.01), by treatment with 1 and 10 μM dopamine, with no differences between either dose as early as 1 h after treatment. The percentage of insulin-positive cells in the islets decreased significantly (p<0.01) after 1 h of treatment up to 12 h. The proliferation rate of insulin-positive cells in the islets decreased significantly (p<0.01) following treatment with dopamine. Apoptosis in pancreatic islets and beta cells was increased by treatment with 1 and 10 μM dopamine along 12 h. In conclusion, these results suggest that dopamine could modulate the proliferation and apoptosis of pancreatic beta cells and that dopamine may be involved in the maintenance of pancreatic islets.
Highlights
Dopamine is a neurotransmitter that plays a critical role in neurological and psychiatric disorders [1] and it is involved in various physiological functions, including modulation of the PLOS ONE | DOI:10.1371/journal.pone.0123197 April 17, 2015Dopamine Regulates the Survival of Pancreatic Beta Cells endocrine system
Several authors consider that dopamine analogues would inhibit glucose-stimulated insulin release [9], whereas others have reported an enhancement of insulin secretion upon acute dopamine accumulation [3]
Treatment with dopamine induced a reduction in insulin release to the medium at all times and for all doses assayed
Summary
Dopamine is a neurotransmitter that plays a critical role in neurological and psychiatric disorders [1] and it is involved in various physiological functions, including modulation of the PLOS ONE | DOI:10.1371/journal.pone.0123197 April 17, 2015Dopamine Regulates the Survival of Pancreatic Beta Cells endocrine system. A single injection of L-dopa results in the accumulation of dopamine in beta cells and the inhibition of insulin secretory responses [7,8]. The literature contains conflicting reports about the effects of dopamine analogues on glucose-stimulated insulin release in isolated islets. Several authors consider that dopamine analogues would inhibit glucose-stimulated insulin release [9], whereas others have reported an enhancement of insulin secretion upon acute dopamine accumulation [3]. These controversies can be explained because different doses of dopamine can induce opposite effects on insulin secretion [10]. Several classical neurotransmitters that act directly on beta cells could function indirectly by enhancing the signals generated by the beta cell glucose-sensing apparatus [11]
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