The Dual Role of Nitric Oxide in Islet β-Cells

Physiology ◽  
1999 ◽  
Vol 14 (2) ◽  
pp. 49-54 ◽  
Author(s):  
Giatgen A. Spinas
Keyword(s):  
Nitric Oxide ◽  
Pancreatic Islets ◽  
Cell Injury ◽  
Signal Transduction Pathway ◽  
Dual Role ◽  
The Other ◽  
Transduction Pathway ◽  
Β Cells ◽  
Β Cell

In pancreatic islets, nitric oxide (NO) produced on exposure to cytokines mediates β-cell injury leading to diabetes mellitus. On the other hand, l-arginine-derived NO may participate in the signal transduction pathway of physiological insulin secretion. This review focuses on the dual role of NO as a mediator of physiological and pathophysiological processes in pancreatic islets.

scholarly journals Unraveling the role of the ghrelin gene peptides in the endocrine pancreas

2010 ◽  
Vol 45 (3) ◽  
pp. 107-118 ◽  
Author(s):  
Riccarda Granata ◽  
Alessandra Baragli ◽  
Fabio Settanni ◽  
Francesca Scarlatti ◽  
Ezio Ghigo
Keyword(s):  
Pancreatic Islets ◽  
Cell Biology ◽  
Islet Cell ◽  
Endocrine Pancreas ◽  
Islet Cells ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Islet Cell ◽  
Ghrelin Gene

The ghrelin gene peptides include acylated ghrelin (AG), unacylated ghrelin (UAG), and obestatin (Ob). AG, mainly produced by the stomach, exerts its central and peripheral effects through the GH secretagogue receptor type 1a (GHS-R1a). UAG, although devoid of GHS-R1a-binding affinity, is an active peptide, sharing with AG many effects through an unknown receptor. Ob was discovered as the G-protein-coupled receptor 39 (GPR39) ligand; however, its physiological actions remain unclear. The endocrine pancreas is necessary for glucose homeostasis maintenance. AG, UAG, and Ob are expressed in both human and rodent pancreatic islets from fetal to adult life, and the pancreas is the major source of ghrelin in the perinatal period. GHS-R1a and GPR39 expression has been shown in β-cells and islets, as well as specific binding sites for AG, UAG, and Ob. Ghrelin colocalizes with glucagon in α-islet cells, but is also uniquely expressed in ε-islet cells, suggesting a role in islet function and development. Indeed, AG, UAG, and Ob regulate insulin secretion in β-cells and isolated islets, promote β-cell proliferation and survival, inhibit β-cell and human islet cell apoptosis, and modulate the expression of genes that are essential in pancreatic islet cell biology. They even induce β-cell regeneration and prevent diabetes in streptozotocin-treated neonatal rats. The receptor(s) mediating their effects are not fully characterized, and a signaling crosstalk has been suggested. The present review summarizes the newest findings on AG, UAG, and Ob expression in pancreatic islets and the role of these peptides on β-cell development, survival, and function.

scholarly journals Modulation of the behavioral and electrical responses to the repellent DEET elicited by the pre-exposure to the same compound inBlattella germanica

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2150 ◽  
Author(s):  
Valeria Sfara ◽  
Gastón A. Mougabure-Cueto ◽  
Paola A. González-Audino
Keyword(s):  
Nitric Oxide ◽  
Electrical Activity ◽  
The Other ◽  
Nitric Oxide Donor ◽  
Chemical Stimulus ◽  
Sensory Adaptation ◽  
Transduction Pathway ◽  
Previous Exposure ◽  
Other Hand

Insects under different stimuli from the environment modify behavioural responses due to changes in the sensitivity of neurons at the peripheral and/or at the central level of the nervous system. This phenomenon is called neuronal plasticity, and sensory adaptation is an example of it. An insect repellent is a chemical that produces oriented movements of the insects away from its source. In this work we studied the modulation of the behavioural and electrical response to the repellent N, N-diethyl-3-methylbenzamide (DEET) in males of the German cockroachB. germanicaproduced by previous exposure to the same repellent.Methods.We determined repellency using a circular arena, one half of which was treated with DEET. The time spent by insects in each half of the arena was measured, and a repellency coefficient (RC) was calculated. The RCs of pre-exposed and non-pre-exposed insects were compared. To determine a possible role of nitric oxide in the modulation of the response to DEET after pre-exposure, the nitric oxide donor S-nitroso-acetyl-cysteine (SNAC) was applied on cockroaches’ antennae. The electrical activity of the cockroaches’ antennae in response to DEET was recorded using electroantennogram (EAG) technique. The response to DEET was recorded also after a long stimulation with the same repellent, and after topical application of SNAC and dbcGMP (a cGMP analogue) on the antennae.Results.We found that previous exposure ofB. germanicamales to the repellent DEET produced an increase of the repellency at the behavioural level, measured as RC. A possible role of nitric oxide (NO) in the transduction pathway of this phenomenon is suggested, since treatment of the cockroaches with the NO donor SNAC also produced an increase of the repellency elicited by DEET. On the other hand, the response of the cockroaches’ antennae exposed to DEET was determined electrophysiologically. The electrical activity in response to DEET decreased when the insects’ antennae were stimulated with a long pulse of the repellent. The activity of the antennae was restored after 10 min. Treatment of the antennae either with SNAC or dbGMPc also produced a decrease in the response of the antennae to the repellent.Discussion.The previous exposure to a chemical stimulus can modify the behaviour associated to the same stimulus, increasing or decreasing the behavioural response. In the case of DEET we found that pre-exposure increased DEET repellency in male cockroaches. We also found NO involvement in a similar phenomenon. On the other hand, the test showed that DEET is perceived by insects’ antennae as an odour. A long exposure of the antennae to DEET caused a transient decrease in the response of the antennae to the same compound. The same effect was achieved by treating the antennae with SNAC or dbcGMP, suggesting the involvement of the NO/cGMP system in the transduction pathway of the sensory adaptation phenomenon elicited by an odour in this species.

scholarly journals Dual Role of Nitric Oxide in Pancreatic β-Cells

2013 ◽  
Vol 123 (4) ◽  
pp. 295-300 ◽  
Author(s):  
Yukiko Kurohane Kaneko ◽  
Tomohisa Ishikawa
Keyword(s):  
Nitric Oxide ◽  
Dual Role ◽  
Β Cells ◽  
Pancreatic Β Cells

Abstract 555: Glucagon-producing Cells are Increased in Mas-deficient Mice

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Janaina F Braga ◽  
Natalia Alenina ◽  
Michael Bader ◽  
Robson A Santos
Keyword(s):  
Pancreatic Islets ◽  
Cell Number ◽  
Metabolic Disturbances ◽  
Β Cells ◽  
Β Cell ◽  
Cell Content ◽  
Pancreatic Morphology ◽  
Overnight Fasting ◽  
Genetic Deletion

Glucagon is produced by the pancreatic α-cells and has an important role in diabetes. Genetic deletion of the angiotensin-(1-7)/receptor Mas is associated with metabolic disturbances. However, the role of Mas in the pancreatic morphology/function is not known. In the present study we investigated the number of pancreatic α-cells and indirectly β-cells number in C57BL/6J and FVB/N Mas-deficient (KO-Mas) mice. After overnight fasting, 12 weeks-old male KO-Mas mice were sacrificed by i.p. administration of ketamin/xylazine. The pancreas was dissected and the splenic part was fixed in formalin for immunohistochemistry analysis. Tissues were cut (5μm thick), with 150μm interval between cuts to obtain different pancreatic islets, and incubated with anti-glucagon primary antibody. Peroxidase activity was visualized by exposing the sections to DAB solution. Ten islets per mouse pancreas were randomly chosen and all the cells present in the islet were counted. After that, each marked α-cell was also counted using a light microscope. The estimated β-cell content was obtained subtracting the total cells from the α-cells. Mas-deficiency resulted in an increase in the number and percentage of the pancreatic α-cell in both backgrounds compared to wild-type mice (C57BL6/J number of α-cell: 146±21 vs. 67±8 in WT, p<0.001; percentage per islet: 17.9±0.91 vs. 12.3±0.9% in WT, p<0.0001; FVB/N number of α-cell: 260±22 vs. 156±12 in WT, p<0.001; percentage per islet: 16±0.8 vs. 10±0.5% in WT, p<0.0001). The estimated β-cell number was not significantly different in both backgrounds. However the percentage of β-cells were reduced in both backgrounds (C57BL6/J: 82.1±0.91 vs. 87.7±0.9%, in WT p<0.0001; FVB/N: 83.53±1.2 vs. 88.6±0.9% in WT, p<0.001). No significant differences were observed in total amount of cells in pancreatic islets, although a trend for increase in Mas-KO was observed. These data suggest that the Mas/Ang-(1-7) axis is important for the maintenance of normal pancreatic morphology. The imbalance of α and β-cell in Mas-KO might be involved in the metabolic alterations produced by Mas deletion, in mice.

Effects of atorvastatin on the regeneration of pancreatic β-cells after streptozotocin treatment in the neonatal rodent

2010 ◽  
Vol 299 (1) ◽  
pp. E92-E100 ◽  
Author(s):  
K. C. Marchand ◽  
E. J. Arany ◽  
D. J. Hill
Keyword(s):  
Endothelial Cells ◽  
Cell Injury ◽  
Cell Mass ◽  
Neonatal Rat ◽  
Neonatal Rats ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
And Control

To investigate the role of statins in β-cell regeneration a model of streptozotocin (STZ)-induced β-cell injury was used in the neonatal rat. We hypothesized that β-cell growth and regeneration would increase following treatment with atorvastatin and that this would be associated with intraislet vasculogenesis. Pregnant Wistar rats were gavaged with 20 or 40 mg/kg atorvastatin for 21 days commencing on gestation day 15. Atorvastatin was detected in the circulation of the offspring. On postnatal day 4, the pups were given either a control or STZ (70 mg/kg ip) injection. β-Cell mass had partially recovered by postnatal day 44 following STZ treatment, and atorvastatin (20 mg/kg) significantly increased β-cell mass in both STZ-treated and control animals. An increase in the numbers of small islets at postnatal day 44 was seen in STZ-treated animals following atorvastatin, suggestive of neogenesis, and glucose tolerance was improved. Treatment with atorvastatin caused an increase in the numbers of intraislet endothelial cells at postnatal day 14 and the percentage of endothelial cells undergoing DNA synthesis, suggesting that angiogenesis had preceded the increase in β-cell mass. The results indicate that functional β-cell mass was expanded with atorvastatin in both control and STZ-treated neonatal rats and suggests a novel effect of a statin in promoting islet plasticity.

scholarly journals Potential Role of NO in Modulation of COX-2 Expression and PGE2 Production in Pancreatic β-cells

2005 ◽  
Vol 37 (2) ◽  
pp. 139-146 ◽  
Author(s):  
Jia-Jian Ling ◽  
Yu-Jie Sun ◽  
Dong-Ya Zhu ◽  
Qi Chen ◽  
Xiao Han
Keyword(s):  
Nitric Oxide ◽  
Protein Expression ◽  
Gene Transcription ◽  
Pge2 Production ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
No Formation ◽  
Cox 2

Abstract Cytokines have been implicated in pancreatic β-cell destruction leading to type 1 diabetes. Exposure to interleukin-1β (IL-1β) of pancreatic β-cells induces expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Subsequent formation of nitric oxide (NO) and prostaglandin E2 (PGE2) may impair β-cell function. Using NOS inhibitor NG-monomethyl-L-arginine (L-NMMA), we have further investigated the relation between NO formation and COX-2 expression. IL-1β stimulated the formation of NO and PGE2 by pancreatic β-cells. L-NMMA completely inhibited IL-1β-induced NO formation and attenuated PGE2 production. COX-2 gene transcription level and protein expression were determined by real-time PCR, Western blot and luciferase analysis. L-NMMA inhibited IL-1β-induced promoter activity, gene transcription and protein expression of COX-2 in pancreatic β-cells. Therefore, we concluded that NO-affected COX-2 activity is directly linked to COX-2 gene transcription and protein expression in pancreatic β-cells. The identification of a novel interaction of NO on the COX signaling pathway in β-cells provides a strategy of intervention for further evaluating the role of NO and PGE2 in autoimmune diabetes.

scholarly journals Dual Role of Nitric Oxide in Regulating the Response of β Cells to DNA Damage

2018 ◽  
Vol 29 (14) ◽  
pp. 1432-1445 ◽  
Author(s):  
Bryndon J. Oleson ◽  
John A. Corbett
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Dual Role ◽  
Β Cells

scholarly journals Regulation of Insulin Secretion and β-Cell Mass by Activating Signal Cointegrator 2

2006 ◽  
Vol 26 (12) ◽  
pp. 4553-4563 ◽  
Author(s):  
Seon-Yong Yeom ◽  
Geun Hyang Kim ◽  
Chan Hee Kim ◽  
Heun Don Jung ◽  
So-Yeon Kim ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Endocrine Cells ◽  
Potential Role ◽  
Cell Mass ◽  
Dominant Negative ◽  
Transcriptional Coactivator ◽  
Β Cells ◽  
Β Cell ◽  
Islet Mass

ABSTRACT Activating signal cointegrator 2 (ASC-2) is a transcriptional coactivator of many nuclear receptors (NRs) and other transcription factors and contains two NR-interacting LXXLL motifs (NR boxes). In the pancreas, ASC-2 is expressed only in the endocrine cells of the islets of Langerhans, but not in the exocrine cells. Thus, we examined the potential role of ASC-2 in insulin secretion from pancreatic β-cells. Overexpressed ASC-2 increased glucose-elicited insulin secretion, whereas insulin secretion was decreased in islets from ASC-2+/− mice. DN1 and DN2 are two dominant-negative fragments of ASC-2 that contain NR boxes 1 and 2, respectively, and block the interactions of cognate NRs with the endogenous ASC-2. Primary rat islets ectopically expressing DN1 or DN2 exhibited decreased insulin secretion. Furthermore, relative to the wild type, ASC-2+/− mice showed reduced islet mass and number, which correlated with increased apoptosis and decreased proliferation of ASC-2+/− islets. These results suggest that ASC-2 regulates insulin secretion and β-cell survival and that the regulatory role of ASC-2 in insulin secretion appears to involve, at least in part, its interaction with NRs via its two NR boxes.

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