Anti-diabetic actions of carbon monoxide-releasing molecule (CORM)-A1: Immunomodulation and regeneration of islet beta cells

Nikolić, Ivana; Saksida, Tamara; Vujičić, Milica; Stojanović, Ivana; Stošić‐Grujičić, Stanislava

doi:10.1016/j.imlet.2015.03.009

Cited by 19 publications

(10 citation statements)

References 43 publications

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“…The effects of CO on β-cell dysfunction are under investigation. Recent studies have shown that pharmacological application of CO ameliorates β-cell dysfunction in type 1 diabetes [39, 40]. Similarly, we observed RuCO had beneficial effects on PA-induced lipotoxicity in INS-1 cells, for example, it reduced ER stress.…”

Section: Discussionsupporting

confidence: 80%

Baicalein protects rat insulinoma INS-1 cells from palmitate-induced lipotoxicity by inducing HO-1

et al. 2017

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Objectiveβ-Cell dysfunction plays a central role in the pathogenesis of type 2 diabetes (T2D), and the identification of novel approaches to improve β-cell function is essential to treat this disease. Baicalein, a flavonoid originally isolated from the root of Scutellaria Baicalensis, has been shown to have beneficial effects on β-cell function. Here, the authors investigated the molecular mechanism responsible for the protective effects of baicalein against palmitate (PA)-induced impaired β-cell function, and placed focus on the role of heme oxygenase (HO)-1.MethodsRat pancreatic β-cell line INS-1 cells or mouse pancreatic islets were cultured with PA (500 μM) to induce lipotoxicity in the presence or absence of baicalein (50 μM), and the expressions of the ER stress markers, ATF-3, CHOP and GRP78 were detected by Western blotting and/or qPCR. The involvement of HO-1 was evaluated by HO-1 siRNA transfection and using the HO-1 inhibitor ZnPP.ResultsBaicalein reduced PA-induced ER stress and inflammation and enhanced insulin secretion, and these effects were associated with the induction of HO-1. Furthermore, these protective effects were attenuated by ZnPP and by HO-1 siRNA. Pretreatment of PD98059 (an ERK inhibitor) significantly inhibited the protective effects of baicalein and blocked HO-1 induction. On the other hand, CO production by RuCO (a CO donor) ameliorated PA-induced ER stress, suggesting that CO production followed by HO-1 induction may contribute to the protective effects of baicalein against PA-induced β-cell dysfunction.ConclusionBaicalein protects pancreatic β-cells from PA-induced ER stress and inflammation via an ERK-HO-1 dependent pathway. The authors suggest HO-1 induction in pancreatic β-cells appears to be a promising therapeutic strategy for T2D.

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Section: Discussionsupporting

confidence: 80%

Baicalein protects rat insulinoma INS-1 cells from palmitate-induced lipotoxicity by inducing HO-1

et al. 2017

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“…CD206, CD163), and whole pancreata showed increased levels of M2-associated genes ( Mrc1/CD206 , Msr1/CD204 , Cx3cr1 ) and anti-inflammatory cytokines (IL-10, TGFβ1) [61]. Additional signaling pathways that may protect β-cells from oxidative damage and stress include activation of carbon monoxide leasing molecule (CORM)-A1 [62], cell cycle-independent effects of cyclin D2 inhibition [63], and cytokine-activated signaling [64,65]. …”

Section: Introductionmentioning

confidence: 99%

Replicative capacity of β-cells and type 1 diabetes

Saunders

Powers

2016

Journal of Autoimmunity

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Efforts to restore β-cell number or mass in type 1 diabetes (T1D) must combine an intervention to stimulate proliferation of remaining β-cells and an intervention to mitigate or control the β-cell-directed autoimmunity. This review highlights features of the β-cell, including it being part of a pancreatic islet, a mini-organ that is highly vascularized and highly innervated, and efforts to promote β-cell proliferation. In addition, the β-cell in T1D exists in a microenvironment with interactions and input from other islet cell types, extracellular matrix, vascular endothelial cells, neuronal projections, and immune cells, all of which likely influence the β-cell’s capacity for replication. Physiologic β-cell proliferation occurs in human and rodents in the neonatal period and early in life, after which there is an age-dependent decline in β-cell proliferation, and also as part of the β-cell’s compensatory response to the metabolic challenges of pregnancy and insulin resistance. This review reviews the molecular pathways involved in this β-cell proliferation and highlights recent work in two areas: 1) Investigators, using high-throughput screening to discover small molecules that promote human β-cell proliferation, are now focusing on the dual-specificity tyrosine-regulated kinase-1a and cell cycle-dependent kinase inhibitors CDKN2C/p18 or CDKN1A/p21 as targets of compounds to stimulate adult human β-cell proliferation. 2) Local inflammation, macrophages, and the local β-cell microenvironment promote β-cell proliferation. Future efforts to harness the responsible mechanisms may lead to new approaches to promote β-cell proliferation in T1D.

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“…It was also observed that CORM treatment reduced the mechanical and thermal hypersensitivity caused by sciatic nerve injury. Next, the effects of CORM-A1 on preventing diabetes via beta cell regeneration were examined by Nikolic et al [ 35 ]. In diabetes, the immune system of the body attacks and destroys the beta cells; this situation is characterized by a high interleukin and T-helper cell count as well as a low TGF-ß count and Ki-67 protein expression.…”

Section: Contributions Of Corms In Nociception and Diabetesmentioning

confidence: 99%

An Overview of the Potential Therapeutic Applications of CO-Releasing Molecules

Ismailova

Kuter

Bohle

et al. 2018

Bioinorganic Chemistry and Applications

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Carbon monoxide (CO) has long been known as the “silent killer” owing to its ability to form carboxyhemoglobin—the main cause of CO poisoning in humans. Its role as an endogenous neurotransmitter, however, was suggested in the early 1990s. Since then, the biological activity of CO has been widely examined via both the direct administration of CO and in the form of so-called “carbon monoxide releasing molecules (CORMs).” This overview will explore the general physiological effects and potential therapeutic applications of CO when delivered in the form of CORMs.

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Anti-diabetic actions of carbon monoxide-releasing molecule (CORM)-A1: Immunomodulation and regeneration of islet beta cells

Cited by 19 publications

References 43 publications

Baicalein protects rat insulinoma INS-1 cells from palmitate-induced lipotoxicity by inducing HO-1

Baicalein protects rat insulinoma INS-1 cells from palmitate-induced lipotoxicity by inducing HO-1

Replicative capacity of β-cells and type 1 diabetes

An Overview of the Potential Therapeutic Applications of CO-Releasing Molecules

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