Nitric oxide involvement in pancreatic β cell apoptosis by glibenclamide

Ansar, Malek Moien; Ansari, Mohammad

doi:10.1016/j.niox.2005.09.002

Cited by 17 publications

(7 citation statements)

References 34 publications

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“…Glibenclamide has been shown to act as both a K ATP channel blocker and a vasorelaxant . Glibenclamide induces NO generation, which is primarily responsible for the glibenclamide‐induced endothelium‐dependent relaxation . If the beneficial effect of nicorandil on attenuated myocardial fibrosis was explained by NO rise, the rats treated with glibenclamide should be expected to have similar myocardial fibrosis compared with nicorandil alone.…”

Section: Discussionmentioning

confidence: 99%

Nicorandil regulates the macrophage skewing and ameliorates myofibroblasts by inhibition of RhoA/Rho‐kinase signalling in infarcted rats

Lee

Lin

Chang

2017

J Cellular Molecular Medi

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We have demonstrated that ATP‐sensitive potassium (KATP) channel agonists attenuated fibrosis; however, the mechanism remained unclear. Since RhoA has been identified as a mediator of cardiac fibrosis, we sought to determine whether the anti‐fibrotic effects of KATP channel agonists were mediated via regulating macrophage phenotype and fibroblast differentiation by a RhoA/RhoA‐kinase‐dependent pathway. Wistar male rats after induction of myocardial infarction were randomized to either vehicle, nicorandil, an antagonist of KATP channel glibenclamide, an antagonist of ROCK fasudil, or a combination of nicorandil and glibenclamide or fasudil and glibenclamide starting 24 hrs after infarction. There were similar infarct sizes among the infarcted groups. At day 3 after infarction, post‐infarction was associated with increased RhoA/ROCK activation, which can be inhibited by administering nicorandil. Nicorandil significantly increased myocardial IL‐10 levels and the percentage of regulatory M2 macrophages assessed by immunohistochemical staining, Western blot, and RT‐PCR compared with vehicle. An IL‐10 receptor antibody increased myofibroblast infiltration compared with nicorandil alone. At day 28 after infarction, nicorandil was associated with attenuated cardiac fibrosis. These effects of nicorandil were functionally translated in improved echocardiographically derived cardiac performance. Fasudil showed similarly increased expression of M2 macrophages as nicorandil. The beneficial effects of nicorandil on fibroblast differentiation were blocked by adding glibenclamide. However, glibenclamide cannot abolish the attenuated fibrosis of fasudil, implying that RhoA/RhoA‐kinase is a downstream effector of KATP channel activation. Nicorandil polarized macrophages into M2 phenotype by inhibiting RhoA/RhoA‐kinase pathway, which leads to attenuated myofibroblast‐induced cardiac fibrosis after myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

Nicorandil regulates the macrophage skewing and ameliorates myofibroblasts by inhibition of RhoA/Rho‐kinase signalling in infarcted rats

Lee

Lin

Chang

2017

J Cellular Molecular Medi

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“…Previous studies have provided conflicting evidence about the pro- or anti-apoptotic role of sulphonylureas, and specifically of glibenclamide [9–11,13], which have been tentatively attributed to a variety of mechanisms. In view of this uncertainty, we revisited the diabetes-prone NOD mice, to assess whether the favourable in vitro effects of glibenclamide could help protecting beta cells in vivo , specifically against the initial autoimmune attack that triggers type 1 diabetes [6,19].…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports have suggested that sulphonylureas may mitigate the hyperglycaemia which develops with age in the non-obese diabetic mice (NOD), a widely used model of type 1 diabetes [7,8]. However, these studies have also provided conflicting evidence about such a protective role [9–11]. Thus, in a second part of this study, we longitudinally monitored NOD mice during a chronic exposure to glibenclamide, starting at an age when the pathological and biological signs of hyperglycemia and diabetes had not yet developed [12].…”

Section: Introductionmentioning

confidence: 99%

Glibenclamide Prevents Diabetes in NOD Mice

et al. 2016

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Previous work has revealed that Cx36, the sole connexin expressed in the insulin-producing beta cells, enhances the secretion of insulin, and promotes the resistance of beta cells against pro-inflammatory cytokines. In parallel, the anti-diabetic sulphonylurea glibenclamide was shown to promote the assembly and function of Cx36 channels. Here, we assessed whether glibenclamide could protect the insulin-producing cells against conditions mimicking those expected at the onset of type 1 diabetes. We found that the drug 1) protected in vitro the mouse MIN6 cells from the apoptosis and loss of Cx36, which are induced by Th1 cytokines; 2) prevented the development of hyperglycemia as well as the loss of beta cells and Cx36, which rapidly develop with aging in untreated NOD mice; 3) modified the proportion of effector CD4+ and CD8+ T cells in pancreatic draining lymph nodes. The data imply that an early glibenclamide treatment may help protecting beta cells against the autoimmune attack, which triggers the development of type 1 diabetes.

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“…One explanation for this negative regulation is activation of AMP-activated protein kinase (AMPK), with the resultant signaling leading to downregulation of pro-secretion pathways and initiation of cytoprotective responses, including upregulation of the unfolded protein response [85]. Yet other investigators provide data suggesting that •NO can initiate cell death processes through multiple mechanisms, such as initiation of apoptosis [86, 87] and interference with zinc homeostasis [88-90]. Given that so many forms of cellular pathology arise when oxidative molecules surpass a given buffering antioxidant threshold, the hypothesis that RNS are uniformly negative signals, serving as protein inhibition and destabilization effectors is quite reasonable as it presents a significant weakness in the beta cell and an opportunity to go awry.…”

Section: Part 3 the Transition From Post-trans-lational Modificationmentioning

confidence: 99%

The Good and Bad Effects of Cysteine S-nitrosylation and Tyrosine Nitration upon Insulin Exocytosis: A Balancing Act

Wiseman

Thurmond²

2012

CDR

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As understanding of the mechanisms driving and regulating insulin secretion from pancreatic beta cells grows, there is increasing and compelling evidence that nitric oxide (•NO) and other closely-related reactive nitrogen species (RNS) play important roles in this exocytic process. •NO and associated RNS, in particular peroxynitrite, possess the capability to effect signals across both intracellular and extracellular compartments in rapid fashion, affording extraordinary signaling potential. It is well established that nitric oxide signals through activation of guanylate cyclase-mediated production of cyclic GMP. The intricate intracellular redox environment, however, lends credence to the possibility that •NO and peroxynitrite could interact with a wider variety of biological targets, with two leading mechanisms involving 1) S-nitrosylation of cysteine, and 2) nitration of tyrosine residues comprised within a variety of proteins. Efforts aimed at delineating the specific roles of •NO and peroxynitrite in regulated insulin secretion indicate that a highly-complex and nuanced system exists, with evidence that •NO and peroxynitrite can contribute in both positive and negative regulatory ways in beta cells. Furthermore, the ultimate biochemical outcome within beta cells, whether to compensate and recover from a given stress, or not, is likely a summation of contributory signals and redox status. Such seeming regulatory dichotomy provides ample opportunity for these mechanisms to serve both physiological and pathophysiologic roles in onset and progression of diabetes. This review focuses attention upon recent accumulating evidence pointing to roles for nitric oxide induced post-translational modifications in the normal regulation as well as the dysfunction of beta cell insulin exocytosis.

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Nitric oxide involvement in pancreatic β cell apoptosis by glibenclamide

Cited by 17 publications

References 34 publications

Nicorandil regulates the macrophage skewing and ameliorates myofibroblasts by inhibition of RhoA/Rho‐kinase signalling in infarcted rats

Nicorandil regulates the macrophage skewing and ameliorates myofibroblasts by inhibition of RhoA/Rho‐kinase signalling in infarcted rats

Glibenclamide Prevents Diabetes in NOD Mice

The Good and Bad Effects of Cysteine S-nitrosylation and Tyrosine Nitration upon Insulin Exocytosis: A Balancing Act

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