Prevention of antipsychotic-induced hyperglycaemia by vitamin D: a data mining prediction followed by experimental exploration of the molecular mechanism

Nagashima, Takuya; Shirakawa, Hisashi; Nakagawa, Takayuki; Kaneko, Shuji

doi:10.1038/srep26375

Cited by 53 publications

(61 citation statements)

References 35 publications

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“…There have been studies using integrative approaches of SSA and DPA to find safety signals [ 25 , 26 ]. In addition, DPA has been utilized to find unknown drug effects, for which several studies on drug repositioning have been reported [ 7 ]. In our study, an integrative approach using SSA and DPA was applied to identify repositioning opportunities for marketed drugs.…”

Section: Methodsmentioning

confidence: 99%

“…Inverse associations generally detected in using SSA and DPA have no meaning and are thus commonly disregarded. However, we noted that inverse associations between target drugs and AEs are often present, which suggest potential alternative therapeutic opportunities [ 7 ]. To our knowledge, there are several reports on evaluation of these inverse associations for their benefits to other methodologies such as drug-repositioning approaches [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…It is the trend now to connect the drug candidate and their potential new applications by data mining of RWD to build the network of pharmacological elements [ 11 ]. DPA has proven useful in finding unknown drug effects [ 7 ]. Recently, we reported that integrative approach using SSA and DPA showed inverse association between sodium channel-blocking antiepileptic drug use and several cancers [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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An integrative approach using real-world data to identify alternative therapeutic uses of existing drugs

et al. 2018

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Different computational approaches are employed to efficiently identify novel repositioning possibilities utilizing different sources of information and algorithms. It is critical to propose high-valued candidate-repositioning possibilities before conducting lengthy in vivo validation studies that consume significant resources. Here we report a novel multi-methodological approach to identify opportunities for drug repositioning. We performed analyses of real-world data (RWD) acquired from the United States Food and Drug Administration’s Adverse Event Reporting System (FAERS) and the claims database maintained by the Japan Medical Data Center (JMDC). These analyses were followed by cross-validation through bioinformatics analyses of gene expression data. Inverse associations revealed using disproportionality analysis (DPA) and sequence symmetry analysis (SSA) were used to detect potential drug-repositioning signals. To evaluate the validity of the approach, we conducted a feasibility study to identify marketed drugs with the potential for treating inflammatory bowel disease (IBD). Primary analyses of the FAERS and JMDC claims databases identified psycholeptics such as haloperidol, diazepam, and hydroxyzine as candidates that may improve the treatment of IBD. To further investigate the mechanistic relevance between hit compounds and disease pathology, we conducted bioinformatics analyses of the associations of the gene expression profiles of these compounds with disease. We identified common biological features among genes differentially expressed with or without compound treatment as well as disease-perturbation data available from open sources, which strengthened the mechanistic rationale of our initial findings. We further identified pathways such as cytokine signaling that are influenced by these drugs. These pathways are relevant to pathologies and can serve as alternative targets of therapy. Integrative analysis of RWD such as those available from adverse-event databases, claims databases, and transcriptome analyses represent an effective approach that adds value to efficiently identifying potential novel therapeutic opportunities.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An integrative approach using real-world data to identify alternative therapeutic uses of existing drugs

et al. 2018

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“…Glucose uptake 2-NBDG uptake was performed as previously described (Nagashima et al, 2016) with some modifications. Cells (3 Â 10 4 cells) were seeded in a 96-well black plate.…”

Section: Subcellular Fractionationmentioning

confidence: 99%

AMPK activation by prolonged stimulation with interleukin‐1β contributes to the promotion of GLUT4 translocation in skeletal muscle cells

Takaguri

Inoué

Kubo

et al. 2016

Cell Biology International

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Impaired insulin signaling in skeletal muscle cells causes insulin resistance associated with the onset of type 2 diabetes. Although interleukin (IL)-1β has been considered to be implicated in the pathogenesis of type 2 diabetes, the action of prolonged stimulation with IL-1β on the insulin signaling pathway in skeletal muscle cells remains poorly understood. In the current study, we investigated the effect of IL-1β stimulation on insulin signal transduction from the insulin receptor (IR), resulting in glucose transporter 4 (GLUT4) translocation in skeletal muscle cells. In L6-GLUT4myc cells, stimulation with IL-1β for 24 h promoted GLUT4 translocation to the plasma membrane and increased glucose uptake in a concentration-dependent manner, whereas short-term stimulation with IL-1 for up to 6 h did not affect that. In addition, stimulation with IL-1β for 24 h further increased insulin-stimulated GLUT4 translocation. Interestingly, stimulation with IL-1β for 24 h did not cause any change in the phosphorylation of insulin signal molecules IR, insulin receptor substrate (IRS)-1, Akt, and p21-activated kinase (PAK1). Stimulation with IL-1β for 24 h significantly increased AMP-activated protein kinase (AMPK) phosphorylation and GLUT4 protein expression. Small interfering RNA (siRNA) targeting AMPK1/2 significantly inhibited IL-1β-stimulated GLUT4 translocation. These results suggest that prolonged stimulation with IL-1β positively regulates GLUT4 translocation in skeletal muscle cells. IL-1β may have a beneficial effect on maintaining glucose homeostasis in skeletal muscle cells in patients with type 2 diabetes. .

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“…But is there any way to utilize shared data in basic studies related to pharmaceutical sciences? In this review, based on our experiences published in 2016, 1) we show how to process clinical evidence for the promotion of basic research, and propose new methods for developing drug discovery.…”

Section: Introductionmentioning

confidence: 99%

Drug Repositioning and Target Finding Based on Clinical Evidence

Kaneko

Nagashima

2020

Biological & Pharmaceutical Bulletin

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Recent pharmacological studies have been developed based on finding new disease-related genes, accompanied by the production of gene-manipulated disease model animals and high-affinity ligands for the target proteins. However, the emergence of this gene-based strategy in drug development has led to the rapid depletion of drug target molecules. To overcome this, we have attempted to utilize clinical big data to explore a novel and unexpected hypothesis of drug-drug interaction that would lead to drug repositioning. Here, we introduce our data-driven approach in which adverse event self-reports are statistically analyzed and compared in order to find and validate new drug targets. The hypotheses provided by such a data-driven approach will likely impact the style of future drug development and pharmaceutical study.

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Prevention of antipsychotic-induced hyperglycaemia by vitamin D: a data mining prediction followed by experimental exploration of the molecular mechanism

Cited by 53 publications

References 35 publications

An integrative approach using real-world data to identify alternative therapeutic uses of existing drugs

An integrative approach using real-world data to identify alternative therapeutic uses of existing drugs

AMPK activation by prolonged stimulation with interleukin‐1β contributes to the promotion of GLUT4 translocation in skeletal muscle cells

Drug Repositioning and Target Finding Based on Clinical Evidence

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