Tetrahydrobiopterin Synthesis Precedes Nitric Oxide-Dependent Inhibition of Insulin Secretion in INS-1 Rat Pancreatic β-Cells

1997 ◽  
Vol 233 (1) ◽  
pp. 66-70 ◽  
Author(s):  
R. Laffranchi ◽  
G. Schoedon ◽  
N. Blau ◽  
G.A. Spinas
Keyword(s):  
Nitric Oxide ◽  
Insulin Secretion ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Dependent Inhibition

scholarly journals Nitric oxide interacts with cholinoceptors to modulate insulin secretion by pancreatic β cells

2020 ◽  
Vol 472 (10) ◽  
pp. 1469-1480
Author(s):  
Bashair M. Mussa ◽  
Ankita Srivastava ◽  
Abdul Khader Mohammed ◽  
Anthony J. M. Verberne
Keyword(s):  
Nitric Oxide ◽  
Insulin Secretion ◽  
Cell Viability ◽  
Combined Treatment ◽  
No Production ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Tnf Α ◽  
Ifn Γ

Abstract Dysfunction of the pancreatic β cells leads to several chronic disorders including diabetes mellitus. Several mediators and mechanisms are known to be involved in the regulation of β cell secretory function. In this study, we propose that cytokine-induced nitric oxide (NO) production interacts with cholinergic mechanisms to modulate insulin secretion from pancreatic β cells. Using a rat insulinoma cell line INS-1, we demonstrated that β cell viability decreases significantly in the presence of SNAP (NO donor) in a concentration- and time-dependent manner. Cell viability was also found to be decreased in the presence of a combined treatment of SNAP with SMN (muscarinic receptor antagonist). We then investigated the impact of these findings on insulin secretion and found a significant reduction in glucose uptake by INS-1 cells in the presence of SNAP and SMN as compared with control. Nitric oxide synthase 3 gene expression was found to be significantly reduced in response to combined treatment with SNAP and SMN suggesting an interaction between the cholinergic and nitrergic systems. The analysis of gene and protein expression further pin-pointed the involvement of M3 muscarinic receptors in the cholinergic pathway. Upon treatment with cytokines, reduced cell viability was observed in the presence of TNF-α and IFN-γ. A significant reduction in insulin secretion was also noted after treatment with TNF-α and IFN-γ and IL1-β. The findings of the present study have shown for the first time that the inhibition of the excitatory effects of cholinergic pathways on glucose-induced insulin secretion may cause β cell injury and dysfunction of insulin secretion in response to cytokine-induced NO production.

Dual effect of nitric oxide on cytosolic Ca2+concentration and insulin secretion in rat pancreatic β-cells

2003 ◽  
Vol 284 (5) ◽  
pp. C1215-C1222 ◽  
Author(s):  
Yukiko Kaneko ◽  
Tomohisa Ishikawa ◽  
Satoshi Amano ◽  
Koichi Nakayama
Keyword(s):  
Nitric Oxide ◽  
Insulin Secretion ◽  
Kinase Inhibitor ◽  
Soluble Guanylate Cyclase ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Dual Effect ◽  
Independent Manner ◽  
No Donor ◽  
Isolated Rat

In isolated rat pancreatic β-cells, the nitric oxide (NO) donor NOC-7 at 1 μM reduced the amplitude of the oscillations of cytosolic Ca2+ concentration ([Ca2+]c) induced by 11.1 mM glucose, and at 10 μM terminated them. In the presence of N G-nitro-l-arginine (l-NNA), however, NOC-7 at 0.5 and 1 μM increased the amplitude of the [Ca2+]c oscillations, although the NO donor at 10 μM still suppressed them. Aqueous NO solution also had a dual effect on the [Ca2+]c oscillations. The soluble guanylate cyclase inhibitor LY-83583 and the cGMP-dependent protein kinase inhibitor KT5823 inhibited the stimulatory effect of NO, and 8-bromo-cGMP increased the amplitude of the [Ca2+]c oscillations. Patch-clamp analyses in the perforated configuration showed that 8-bromo-cGMP inhibited whole cell ATP-sensitive K+ currents in the isolated rat pancreatic β-cells, suggesting that the inhibition by cGMP of ATP-sensitive K+ channels is, at least in part, responsible for the stimulatory effect of NO on the [Ca2+]c oscillations. In the presence ofl-NNA, the glucose-induced insulin secretion from isolated islets was facilitated by 0.5 μM NOC-7, whereas it was suppressed by 10 μM NOC-7. These results suggest that NO facilitates glucose-induced [Ca2+]c oscillations of β-cells and insulin secretion at low concentrations, which effects are mediated by cGMP, whereas NO inhibits them in a cGMP-independent manner at high concentrations.

scholarly journals A Neuronal Isoform of Nitric Oxide Synthase Expressed in Pancreatic β-Cells Controls Insulin Secretion

Diabetes ◽  
2001 ◽  
Vol 50 (6) ◽  
pp. 1311-1323 ◽  
Author(s):  
Anne-Dominique Lajoix ◽  
Hubbert Reggio ◽  
Thierry Chardès ◽  
Sylvie Péraldi-Roux ◽  
Florence Tribillac ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Secretion ◽  
Nitric Oxide Synthase ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Oxide Synthase

scholarly journals IL-1β reciprocally regulates chemokine and insulin secretion in pancreatic β-cells via NF-κB

2015 ◽  
Vol 309 (8) ◽  
pp. E715-E726 ◽  
Author(s):  
Susan J. Burke ◽  
Krisztian Stadler ◽  
Danhong Lu ◽  
Evanna Gleason ◽  
Anna Han ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Secretion ◽  
Transcriptional Activity ◽  
Cell Function ◽  
Inflammatory Responses ◽  
Cell Mass ◽  
Negative Regulator ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells

Proinflammatory cytokines impact islet β-cell mass and function by altering the transcriptional activity within pancreatic β-cells, producing increases in intracellular nitric oxide abundance and the synthesis and secretion of immunomodulatory proteins such as chemokines. Herein, we report that IL-1β, a major mediator of inflammatory responses associated with diabetes development, coordinately and reciprocally regulates chemokine and insulin secretion. We discovered that NF-κB controls the increase in chemokine transcription and secretion as well as the decrease in both insulin secretion and proliferation in response to IL-1β. Nitric oxide production, which is markedly elevated in pancreatic β-cells exposed to IL-1β, is a negative regulator of both glucose-stimulated insulin secretion and glucose-induced increases in intracellular calcium levels. By contrast, the IL-1β-mediated production of the chemokines CCL2 and CCL20 was not influenced by either nitric oxide levels or glucose concentration. Instead, the synthesis and secretion of CCL2 and CCL20 in response to IL-1β were dependent on NF-κB transcriptional activity. We conclude that IL-1β-induced transcriptional reprogramming via NF-κB reciprocally regulates chemokine and insulin secretion while also negatively regulating β-cell proliferation. These findings are consistent with NF-κB as a major regulatory node controlling inflammation-associated alterations in islet β-cell function and mass.

Congenital hyperinsulinism due to compound heterozygous mutations in ABCC8 responsive to diazoxide therapy

2020 ◽  
Vol 33 (5) ◽  
pp. 671-674
Author(s):  
Tashunka Taylor-Miller ◽  
Jayne Houghton ◽  
Paul Munyard ◽  
Yadlapalli Kumar ◽  
Clinda Puvirajasinghe ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Compound Heterozygous ◽  
Congenital Hyperinsulinism ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Newborn Period ◽  
Case Presentation ◽  
Male Baby ◽  
Common Causes ◽  
Compound Heterozygous Mutations

AbstractBackgroundCongenital hyperinsulinism (CHI), a condition characterized by dysregulation of insulin secretion from the pancreatic β cells, remains one of the most common causes of hyperinsulinemic, hypoketotic hypoglycemia in the newborn period. Mutations in ABCC8 and KCNJ11 constitute the majority of genetic forms of CHI.Case presentationA term macrosomic male baby, birth weight 4.81 kg, born to non-consanguineous parents, presented on day 1 of life with severe and persistent hypoglycemia. The biochemical investigations confirmed a diagnosis of CHI. Diazoxide was started and progressively increased to 15 mg/kg/day to maintain normoglycemia. Sequence analysis identified compound heterozygous mutations in ABCC8 c.4076C>T and c.4119+1G>A inherited from the unaffected father and mother, respectively. The mutations are reported pathogenic. The patient is currently 7 months old with a sustained response to diazoxide.ConclusionsBiallelic ABCC8 mutations are known to result in severe, diffuse, diazoxide-unresponsive hypoglycemia. We report a rare patient with CHI due to compound heterozygous mutations in ABCC8 responsive to diazoxide.

scholarly journals Author Correction: CD44 variant inhibits insulin secretion in pancreatic β cells by attenuating LAT1-mediated amino acid uptake

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Nana Kobayashi ◽  
Shogo Okazaki ◽  
Oltea Sampetrean ◽  
Junichiro Irie ◽  
Hiroshi Itoh ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Amino Acid ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Cd44 Variant

scholarly journals D2-Like Receptors Mediate Dopamine-Inhibited Insulin Secretion via Ion Channels in Rat Pancreatic β-Cells

2020 ◽  
Vol 11 ◽  
Author(s):  
Mengmeng Liu ◽  
Lele Ren ◽  
Xiangqin Zhong ◽  
Yaqin Ding ◽  
Tao Liu ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Ion Channels ◽  
Β Cells ◽  
Pancreatic Β Cells

Jiawei Erzhiwan improves menopausal metabolic syndrome by enhancing insulin secretion in pancreatic β cells

2016 ◽  
Vol 14 (11) ◽  
pp. 823-834 ◽  
Author(s):  
Xiao-Meng WAN ◽  
Mu ZHANG ◽  
Pei ZHANG ◽  
Zhi-Shen XIE ◽  
Feng-Guo XU ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Secretion ◽  
Β Cells ◽  
Pancreatic Β Cells
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