Dopamine Modulates Insulin Release and Is Involved in the Survival of Rat Pancreatic Beta Cells

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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.

Related collections

Most cited references 43

Record: found
Abstract: found
Article: not found

Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities.

Miriam Cnop, Nils Welsh, Jean-Christophe Jonas … (2005)

Type 1 and type 2 diabetes are characterized by progressive beta-cell failure. Apoptosis is probably the main form of beta-cell death in both forms of the disease. It has been suggested that the mechanisms leading to nutrient- and cytokine-induced beta-cell death in type 2 and type 1 diabetes, respectively, share the activation of a final common pathway involving interleukin (IL)-1beta, nuclear factor (NF)-kappaB, and Fas. We review herein the similarities and differences between the mechanisms of beta-cell death in type 1 and type 2 diabetes. In the insulitis lesion in type 1 diabetes, invading immune cells produce cytokines, such as IL-1beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. IL-1beta and/or TNF-alpha plus IFN-gamma induce beta-cell apoptosis via the activation of beta-cell gene networks under the control of the transcription factors NF-kappaB and STAT-1. NF-kappaB activation leads to production of nitric oxide (NO) and chemokines and depletion of endoplasmic reticulum (ER) calcium. The execution of beta-cell death occurs through activation of mitogen-activated protein kinases, via triggering of ER stress and by the release of mitochondrial death signals. Chronic exposure to elevated levels of glucose and free fatty acids (FFAs) causes beta-cell dysfunction and may induce beta-cell apoptosis in type 2 diabetes. Exposure to high glucose has dual effects, triggering initially "glucose hypersensitization" and later apoptosis, via different mechanisms. High glucose, however, does not induce or activate IL-1beta, NF-kappaB, or inducible nitric oxide synthase in rat or human beta-cells in vitro or in vivo in Psammomys obesus. FFAs may cause beta-cell apoptosis via ER stress, which is NF-kappaB and NO independent. Thus, cytokines and nutrients trigger beta-cell death by fundamentally different mechanisms, namely an NF-kappaB-dependent mechanism that culminates in caspase-3 activation for cytokines and an NF-kappaB-independent mechanism for nutrients. This argues against a unifying hypothesis for the mechanisms of beta-cell death in type 1 and type 2 diabetes and suggests that different approaches will be required to prevent beta-cell death in type 1 and type 2 diabetes.

0 comments Cited 296 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Chronic hyperglycemia triggers loss of pancreatic beta cell differentiation in an animal model of diabetes.

R Laybutt, Jeffrey Bonner, Arun Sharma … (1999)

Differentiated pancreatic beta cells are unique in their ability to secrete insulin in response to a rise in plasma glucose. We have proposed that the unique constellation of genes they express may be lost in diabetes due to the deleterious effect of chronic hyperglycemia. To test this hypothesis, Sprague-Dawley rats were submitted to a 85-95% pancreatectomy or sham pancreatectomy. One week later, the animals developed mild to severe chronic hyperglycemia that was stable for the next 3 weeks, without significant alteration of plasma nonesterified fatty acid levels. Expression of many genes important for glucose-induced insulin release decreased progressively with increasing hyperglycemia, in parallel with a reduction of several islet transcription factors involved in beta cell development and differentiation. In contrast, genes barely expressed in sham islets (lactate dehydrogenase A and hexokinase I) were markedly increased, in parallel with an increase in the transcription factor c-Myc, a potent stimulator of cell growth. These abnormalities were accompanied by beta cell hypertrophy. Changes in gene expression were fully developed 2 weeks after pancreatectomy. Correction of blood glucose by phlorizin for the next 2 weeks normalized islet gene expression and beta cell volume without affecting plasma nonesterified fatty acid levels, strongly suggesting that hyperglycemia triggers these abnormalities. In conclusion, chronic hyperglycemia leads to beta cell hypertrophy and loss of beta cell differentiation that is correlated with changes in c-Myc and other key transcription factors. A similar change in beta cell differentiation could contribute to the profound derangement of insulin secretion in human diabetes.

0 comments Cited 108 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The molecular mechanisms of pancreatic β-cell glucotoxicity: recent findings and future research directions.

Mohammed Bensellam, D. Laybutt, Jean-Christophe Jonas (2012)

It is well established that regular physiological stimulation by glucose plays a crucial role in the maintenance of the β-cell differentiated phenotype. In contrast, prolonged or repeated exposure to elevated glucose concentrations both in vitro and in vivo exerts deleterious or toxic effects on the β-cell phenotype, a concept termed as glucotoxicity. Evidence indicates that the latter may greatly contribute to the pathogenesis of type 2 diabetes. Through the activation of several mechanisms and signaling pathways, high glucose levels exert deleterious effects on β-cell function and survival and thereby, lead to the worsening of the disease over time. While the role of high glucose-induced β-cell overstimulation, oxidative stress, excessive Unfolded Protein Response (UPR) activation, and loss of differentiation in the alteration of the β-cell phenotype is well ascertained, at least in vitro and in animal models of type 2 diabetes, the role of other mechanisms such as inflammation, O-GlcNacylation, PKC activation, and amyloidogenesis requires further confirmation. On the other hand, protein glycation is an emerging mechanism that may play an important role in the glucotoxic deterioration of the β-cell phenotype. Finally, our recent evidence suggests that hypoxia may also be a new mechanism of β-cell glucotoxicity. Deciphering these molecular mechanisms of β-cell glucotoxicity is a mandatory first step toward the development of therapeutic strategies to protect β-cells and improve the functional β-cell mass in type 2 diabetes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

0 comments Cited 95 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Matthias G von Herrath: Role: Academic Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 17 April 2015

Publication date Collection: 2015

Volume: 10

Issue: 4

Electronic Location Identifier: e0123197

Affiliations

[1 ]Department of Physiology and Pharmacology, Faculty of Medicine, University of Salamanca, Salamanca, Spain

[2 ]Department of Human Anatomy and Histology, Faculty of Medicine, University of Salamanca, Salamanca, Spain

[3 ]Laboratory of Neuroendocrinology, Institute of Neurosciences of Castilla y León, and Laboratory of Neuroendocrinology and Obesity of IBSAL, University of Salamanca, Salamanca, Spain

La Jolla Institute for Allergy and Immunology, UNITED STATES

Author notes

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: JC MJGB. Performed the experiments: MJGB MCIO EJB MCH VSR LC JC SC. Analyzed the data: MJGB MCIO EJB JC SC. Contributed reagents/materials/analysis tools: MJGB MCH VSR LC JC. Wrote the paper: JC MJGB.

* E-mail: jcar@ 123456usal.es

Article

Publisher ID: PONE-D-14-54585

DOI: 10.1371/journal.pone.0123197

PMC ID: 4401745

PubMed ID: 25886074

SO-VID: 36ce14ac-39e4-4570-bdf7-625550c479c6

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

History

Date received : 5 December 2014

Date accepted : 18 February 2015

Page count

Figures: 5, Tables: 0, Pages: 16

Funding

This work was supported by Junta de Castilla y León grant BIO103/SA18/11. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Custom metadata

Data Availability All relevant data are within the paper and its Supporting Information files.

Dopamine Modulates Insulin Release and Is Involved in the Survival of Rat Pancreatic Beta Cells

Read this article at

Abstract

Related collections

PLOS Climate

Most cited references 43

Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities.

Chronic hyperglycemia triggers loss of pancreatic beta cell differentiation in an animal model of diabetes.

The molecular mechanisms of pancreatic β-cell glucotoxicity: recent findings and future research directions.

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Page count

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 208

Cited by 14

Most referenced authors 603