Novel Culture Technique Involving an Histone Deacetylase Inhibitor Reduces the Marginal Islet Mass to Correct Streptozotocin-Induced Diabetes

Shin, Juyeon; Min, Bon Hong; Lim, Jong Yeon; Kim, Byoung Keun; Han, Hyun Ju; Yoon, Kun Ho; Kim, Sang Joon; Park, Chung Gyu

doi:10.3727/096368910x557146

Cited by 11 publications

(8 citation statements)

References 55 publications

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“…Enhancing effects of TSA on βTC-tet cells in this study are in accordance with reports of a dose-dependent increase in insulin secretion from human islets treated with VPA (10) and increased insulin secretion after the use of a culture technique on rat islets involving 0.1 μM TSA treatment for 24 hours (9). The effects of TSA alone on rat islets in the latter study, however, were not assessed and results from the former study were attributed to the structural similarity of VPA to free fatty acid secretagogues.…”

Section: Discussionsupporting

confidence: 93%

“…As β-cell function is critical for proper blood glucose regulation, investigating direct HDACi effects on β-cell function is vital toward developing a clinically acceptable treatment. Some studies have observed HDACi effects on β-cell line or islet function, but as an aside to their primary investigation of anti-inflammatory effects (3, 4) or a pre-culture method for improved islet transplantation (9). So far, the reported effects have been contradictory.…”

Section: Introductionmentioning

confidence: 99%

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Trichostatin A affects the secretion pathways of beta and intestinal endocrine cells

Tiernan

Champion

Sambanis

2015

Experimental Cell Research

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Histone deacetylase inhibitors (HDACi) were recently identified as having significant clinical potential in reversing β-cell functional inhibition caused by inflammation, a shared precursor of Type 1 and Type 2 diabetes. However, HDACi are highly complex and little is known of their direct effect on important cell secretion pathways for blood glucose regulation. The aims of the present study were to investigate the effect of HDACi on insulin secretion from β-cells, GLP-1 secretion from L-cells, and recombinant insulin secretion from engineered L-cells. The β-cell line βTC-tet, L-cell line GLUTag, or recombinant insulin-secreting L-cell lines were exposed to Trichostatin A for 24 hours. Effects on insulin or GLP-1 mRNA, intracellular protein content, processing efficiency, and secretion were measured by real-time PCR, ELISA, and radioimmunoassay. HDACi increased secretion per viable cell in a dose-dependent manner for all cell types. Effects on mRNA levels were variable, but enhanced intracellular polypeptide content and secretion were comparable among cell types. Enhanced recombinant insulin secretion was sustained for seven days in alginate microencapsulated L-cells. HDACi enhances β- and L-cell secretion fluxes in a way that could significantly improve blood glucose regulation in diabetes patients and holds potential as a novel method for enhancing insulin-secreting non-β or β-cell grafts.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Trichostatin A affects the secretion pathways of beta and intestinal endocrine cells

Tiernan

Champion

Sambanis

2015

Experimental Cell Research

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“…The ability to monitor, quantitatively, islet volume within encapsulation systems has been proposed as a method for tracking islet survival and function. 53,54 Our results suggest that further development of XPC for in vivo imaging could provide an important new tool for monitoring encapsulated islets.…”

Section: Discussionmentioning

confidence: 81%

“…53,54 Quantitative data can be extracted from the XPC mCT volume images, allowing determination of islet volume in the beads. The mean volume determined from XPC refraction images was 1.7 -0.08 · 10 5 mm 3 .…”

Section: Xpc Of Microbeads Preimplantationmentioning

confidence: 99%

Imaging of Hydrogel Microsphere Structure and Foreign Body Response Based on Endogenous X-Ray Phase Contrast

Appel

Ibarra

Somo

et al. 2016

Tissue Engineering Part C: Methods

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Transplantation of functional islets encapsulated in stable biomaterials has the potential to cure Type I diabetes. However, the success of these materials requires the ability to quantitatively evaluate their stability. Imaging techniques that enable monitoring of biomaterial performance are critical to further development in the field. Xray phase-contrast (XPC) imaging is an emerging class of X-ray techniques that have shown significant promise for imaging biomaterial and soft tissue structures. In this study, XPC imaging techniques are shown to enable three dimensional (3D) imaging and evaluation of islet volume, alginate hydrogel structure, and local soft tissue features ex vivo. Rat islets were encapsulated in sterile ultrapurified alginate systems produced using a highthroughput microfluidic system. The encapsulated islets were implanted in omentum pouches created in a rodent model of type 1 diabetes. Microbeads were imaged with XPC imaging before implantation and as whole tissue samples after explantation from the animals. XPC microcomputed tomography (mCT) was performed with systems using tube-based and synchrotron X-ray sources. Islets could be identified within alginate beads and the islet volume was quantified in the synchrotron-based mCT volumes. Omental adipose tissue could be distinguished from inflammatory regions resulting from implanted beads in harvested samples with both XPC imaging techniques. Individual beads and the local encapsulation response were observed and quantified using quantitative measurements, which showed good agreement with histology. The 3D structure of the microbeads could be characterized with XPC imaging and failed beads could also be identified. These results point to the substantial potential of XPC imaging as a tool for imaging biomaterials in small animal models and deliver a critical step toward in vivo imaging.

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“…HDAC6 inhibition by TSA or tubacin (an HDAC6 selective inhibitor) can also prevent ischemia and reperfusion-induced retinal neurodegeneration [246]. GLP-1 treatment has been reported to alleviate diabetic retinopathy by inhibiting hyperglycemia-provoked autophagy in the retina of T2D rats mediated through the restoration of GLP-1R expression and HDAC6 inhibition [247]. 5-aza-2'deoxycytidine and TSA, two pan-HDACis, were found to protect human retinal endothelial cells and retinal pigment epithelial cells from toxic effects of hyperglycemic stimuli in vitro by reciprocating high glucose-induced suppression of pigment epithelium-derived factor and counteracting with inflammatory factors [248].…”

Section: Hdac-mediated Therapeutic Options In Diabetic Retinopathymentioning

confidence: 99%

The Emerging role of HDACs: Pathology and Therapeutic targets in Diabetes Mellitus

Dewanjee¹,

Vallamkondu²,

Chakraborty³

et al. 2021

Preprint

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Diabetes mellitus (DM) is one of the principal manifestations of metabolic syndrome and its prevalence with modern lifestyle is increasing incessantly. Chronic hyperglycemia can induce several vascular complications that were referred to be the major cause of morbidity and mortality in DM. Although several therapeutic targets have been identified and accessed clinically, the imminent risk of DM and its prevalence are still ascending. Substantial pieces of evidence revealed that histone deacetylase (HDAC) isoforms can regulate various molecular activities in DM via epigenetic and post-translational regulation of several transcription factors. To date, 18 HDAC isoforms have been identified in mammals that were categorized into 4 different classes. Classes I, II, and IV are regarded as classical HDACs, which operate through a Zn-based mechanism. In contrast, class III HDACs or Sirtuins depend on nicotinamide adenine dinucleotide (NAD+) for their molecular activity. Functionally, most of the HDAC isoforms can regulate β cell fate, insulin release, insulin expression and signaling, and glucose metabolism. Moreover, the roles of HDAC members have been implicated in the regulation of oxidative stress, inflammation, apoptosis, fibrosis, and other pathological events, which substantially contribute to diabetes-related vascular dysfunctions. Therefore, HDACs could serve as the potential therapeutic target in DM towards developing novel intervention strategies. This review sheds light on the emerging role of HDACs/isoforms in diabetic pathophysiology and emphasized the scope of their targeting in DM for constituting the novel interventional strategies for metabolic disorders/complications.

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Novel Culture Technique Involving an Histone Deacetylase Inhibitor Reduces the Marginal Islet Mass to Correct Streptozotocin-Induced Diabetes

Cited by 11 publications

References 55 publications

Trichostatin A affects the secretion pathways of beta and intestinal endocrine cells

Trichostatin A affects the secretion pathways of beta and intestinal endocrine cells

Imaging of Hydrogel Microsphere Structure and Foreign Body Response Based on Endogenous X-Ray Phase Contrast

The Emerging role of HDACs: Pathology and Therapeutic targets in Diabetes Mellitus

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