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Pyruvate kinase M2 overexpression in podocytes ameliorates nephropathy in diabetic mice
Elevated expression of pyruvate kinase isoform M2 (PKM2) in the renal glomeruli of people with diabetes is associated with protection from nephropathy even with hyperglycemia. Furthermore, systemic use of PKM2 activators (TEPP46) can prevent or reverse glomerular pathology in diabetic mice. To determine specifically the role of PKM2 in the development or progression of diabetic glomerulopathy, we generated transgenic mice overexpressing PKM2 specific targeted to the podocytes (PPKM2Tg mice) driven by the podocin promoter. Analysis of the glomeruli from these mice showed 1.5-fold increases in mRNA and protein levels without changes in PKM1, compared to wild type (WT) littermates (p<0.05). Pyruvate kinase (PK) activity in the glomeruli of the PPKM2Tg mice was increased by 40% compared to those in WT mice (p<0.05). Diabetes was induced in eight-week-old WT and PPKM2Tg mice by streptozotocin (STZ) and maintained with sustained glucose levels >400mg/dL for 7 months. Diabetic PPKM2Tg mice showed significantly lower urinary albumin-creatinine ratio (ACR) and kidney weight-body weight ratios (p<0.05) compared to diabetic WT mice even with similar hyperglycemia. PK activity was lowered in the glomeruli of diabetic WT mice by 30%, whereas levels in diabetic PPKM2Tg mice were comparable to non-diabetic WT mice. For renal pathology, diabetic PPKM2Tg mice exhibited smaller glomeruli compared to diabetic WT mice. Similarly, expressions of inflammatory genes including TNF and MCP-1, and fibrotic genes including fibronectin and TGF-1 were downregulated in the glomeruli of diabetic PPKM2Tg mice compared to diabetic WT mice. In contrast, mitochondrial genes such as PGC-1α, Opa1, and cytochrome b in the glomeruli of diabetic PPKM2Tg mice were significantly upregulated as compared to diabetic WT mice. These findings strongly suggest that upregulation or activation of PKM2 and glycolysis may improve mitochondrial function in podocytes and prevent the progression of diabetic nephropathy.

Pyruvate kinase M2 overexpression in podocytes ameliorates nephropathy in diabetic mice
Elevated expression of pyruvate kinase isoform M2 (PKM2) in the renal glomeruli of people with diabetes is associated with protection from nephropathy even with hyperglycemia. Furthermore, systemic use of PKM2 activators (TEPP46) can prevent or reverse glomerular pathology in diabetic mice. To determine specifically the role of PKM2 in the development or progression of diabetic glomerulopathy, we generated transgenic mice overexpressing PKM2 specific targeted to the podocytes (PPKM2Tg mice) driven by the podocin promoter. Analysis of the glomeruli from these mice showed 1.5-fold increases in mRNA and protein levels without changes in PKM1, compared to wild type (WT) littermates (p<0.05). Pyruvate kinase (PK) activity in the glomeruli of the PPKM2Tg mice was increased by 40% compared to those in WT mice (p<0.05). Diabetes was induced in eight-week-old WT and PPKM2Tg mice by streptozotocin (STZ) and maintained with sustained glucose levels >400mg/dL for 7 months. Diabetic PPKM2Tg mice showed significantly lower urinary albumin-creatinine ratio (ACR) and kidney weight-body weight ratios (p<0.05) compared to diabetic WT mice even with similar hyperglycemia. PK activity was lowered in the glomeruli of diabetic WT mice by 30%, whereas levels in diabetic PPKM2Tg mice were comparable to non-diabetic WT mice. For renal pathology, diabetic PPKM2Tg mice exhibited smaller glomeruli compared to diabetic WT mice. Similarly, expressions of inflammatory genes including TNF and MCP-1, and fibrotic genes including fibronectin and TGF-1 were downregulated in the glomeruli of diabetic PPKM2Tg mice compared to diabetic WT mice. In contrast, mitochondrial genes such as PGC-1α, Opa1, and cytochrome b in the glomeruli of diabetic PPKM2Tg mice were significantly upregulated as compared to diabetic WT mice. These findings strongly suggest that upregulation or activation of PKM2 and glycolysis may improve mitochondrial function in podocytes and prevent the progression of diabetic nephropathy.

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Diabetes  

Insulin resistance and hyperglycemia are risk factors for periodontitis and poor wound healing in diabetes, which have been associated with selective loss of insulin- activation of the PI3K/Akt pathway in the gingiva. This study showed that insulin resistance in the mouse gingiva due to selective deletion of smooth muscle and fibroblast insulin receptor (SMIRKO mice) or systemic metabolic changes induced by high fat diet (HFD) in HFD-fed mice exacerbated periodontitis-induced alveolar bone loss, preceded by delayed neutrophil and monocyte recruitment and impaired bacterial clearance compared to their respective controls. The immunocytokines, CXCL1, CXCL2, MCP-1, TNFα, IL-1β and IL-17A exhibited delayed maximal expression in the gingiva of male SMIRKO and HFD-fed mice compared to controls. Targeted overexpression of CXCL1 in the gingiva by adenovirus normalized neutrophil and monocyte recruitment and prevented bone loss in both mouse models of insulin resistance. Mechanistically, insulin enhanced bacterial lipopolysaccharide-induced CXCL1 production in mouse and human gingival fibroblasts (GFs), via Akt pathway and NF-κB activation, which were reduced in GFs from SMIRKO and HFD-fed mice. These results provided the first report that insulin signaling can enhance endotoxin induced CXCL1 expression to modulate neutrophil recruitment, suggesting CXCL1 as a new therapeutic direction for periodontitis or wound healing in diabetes.

DOI： 10.2337/db22-1014

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Aims

Pancreatic β-cell apoptosis may be involved in the onset and progression of type 2 diabetes mellitus, although its mechanism remains unclear. We previously demonstrated that macrophage-derived interferon (IFN) β induced X-linked inhibitor of apoptosis–associated factor 1 (XAF1) expression in β-cells and accelerated β-cell apoptosis in vitro. Here, we explored the effects of XAF1 on β-cell function and progression of diabetes in vivo.

Methods

Pancreatic β-cell-selective XAF1 overexpressing (Xaf1 Tg) mice were generated. Xaf1 Tg mice and their wild-type (WT) littermates were fed either a normal diet or a 40% or 60% high-fat diet (HFD). The effects of β-cell XAF1 on β-cell apoptosis and exacerbation of diabetes were investigated.

Results

Palmitic acid induced IFNβ expression in macrophages, and HFD intake promoted macrophage infiltration in pancreatic islets, both of which cooperatively upregulated XAF1 expression in mouse islets. Furthermore, HFD-fed Xaf1 Tg mice demonstrated increased β-cell apoptosis, lowered insulin expression, and impaired glucose tolerance compared with WT mice fed the same diet. These effects were more pronounced in the 60%HFD group than in the 40%HFD group.

Conclusions

Pancreatic β-cell XAF1 expression was enhanced via HFD-induced, macrophage-derived IFNβ, which promoted β-cell apoptosis and led to a reduction in insulin secretion and progression of diabetes. To our knowledge, this is the first report to demonstrate an association between pancreatic β-cell XAF1 overexpression and exacerbation of diabetes, thus providing insight into the mechanism of β-cell mass reduction in diabetes.

DOI： 10.1007/s00592-022-01930-y

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Other Link： https://link.springer.com/article/10.1007/s00592-022-01930-y/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer  

Immunoregulatory properties of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are promising. Gingival tissue-derived MSCs (GMSCs) have unique immunoregulatory capacity and secrete large amounts of EVs. Recent findings suggest that priming MSCs with inflammatory stimuli is an effective strategy for cell-free therapy. However, the precise mechanism by which the contents of EVs are customized has not been fully elucidated. Here, we show that EVs derived from GMSCs primed with a combination of two pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interferon-α (IFN-α), synergistically promote anti-inflammatory M2 macrophage polarization by increasing the expression of cluster of differentiation 73 (CD73) and CD5 molecule-like (CD5L). Expression of CD73 by TNF-α/IFN-α stimulation was transcriptionally upregulated by the activation of mammalian target of rapamycin signaling and nuclear translocation of hypoxia-inducible factor 1α in GMSCs. TNF-α/IFN-α treatment also significantly increased the expression of CD5L mRNA via the transcription factor DNA-binding protein inhibitor ID3 and liver X receptor. Interestingly, exosomal CD5L is a prerequisite for the synergistic effect of EVs-mediated M2 macrophage polarization. These results indicate that combined pre-licensing with TNF-α and IFN-α in GMSCs is ideal for enhancing the anti-inflammatory function of EVs, which contributes to the establishment of a therapeutic tool.

DOI： 10.1038/s41598-022-17692-0

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Circulation Research  

BACKGROUND: Insulin resistance (IR) can increase atherosclerotic and cardiovascular risk by inducing endothelial dysfunction, decreasing nitric oxide (NO) production, and accelerating arterial inflammation. The aim is to determine the mechanism by which insulin action and NO production in endothelial cells can improve systemic bioenergetics and decrease atherosclerosis via differentiation of perivascular progenitor cells (PPCs) into brown adipocytes (BAT). METHODS: Studies used various endothelial transgenic and deletion mutant ApoE-/- mice of insulin receptors, eNOS (endothelial NO synthase) and ETB (endothelin receptor type B) receptors for assessments of atherosclerosis. Cells were isolated from perivascular fat and micro-vessels for studies on differentiation and signaling mechanisms in responses to NO, insulin, and lipokines from BAT. RESULTS: Enhancing insulin's actions on endothelial cells and NO production in ECIRS1 transgenic mice reduced body weight and increased systemic energy expenditure and BAT mass and activity by inducing differentiation of PPCs into beige/BAT even with high-fat diet. However, positive changes in bioenergetics, BAT differentiation from PPCs and weight loss were inhibited by N(gamma)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of eNOS, in ECIRS1 mice and eNOSKO mice. The mechanism mediating NO's action on PPC differentiation into BAT was identified as the activation of solubilized guanylate cyclase/cGMP protein-dependent kinase Iα/GSK3β (glycogen synthase kinase 3β) pathways. Plasma lipidomics from ECIRS1 mice with NO-induced increased BAT mass revealed elevated 12,13-diHOME production. Infusion of 12,13-diHOME improved endothelial dysfunction and decreased atherosclerosis, whereas its reduction had opposite effects in ApoE-/-mice. CONCLUSIONS: Activation of eNOS and endothelial cells by insulin enhanced the differentiation of PPC to BAT and its lipokines and improved systemic bioenergetics and atherosclerosis, suggesting that endothelial dysfunction is a major contributor of energy disequilibrium in obesity.

DOI： 10.1161/CIRCRESAHA.121.319582

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：JCI Insight  

Diabetic nephropathy (DN) arises from systemic and local changes in glucose metabolism and hemodynamics. We have reported that many glycolytic and mitochondrial enzymes, such as pyruvate kinase M2 (PKM2), were elevated in renal glomeruli of DN-protected type 1 and type 2 diabetic patients. Here, mice with PKM2-specific overexpression in podocytes (PPKM2Tg) were generated to uncover its renal protective function as potential therapeutic target, which prevented elevated albumin-creatinine ratio (ACR), mesangial expansion, basement membrane thickness and podocyte foot process effacement after 7-months of STZ-induced diabetes. Further, diabetes-induced impairment of glycolytic rate and mitochondrial function were normalized in diabetic PPKM2Tg glomeruli, in concordance with elevated Ppargc1a and Vegf expressions. Restored VEGF expression improved glomerular maximal mitochondrial function in diabetic PPKM2Tg and WT mice. Elevated VEGF levels were observed in the glomeruli of DN-protected patients with chronic type 1 diabetes, and clinically correlated with estimated GFR, but not glycemic control. Mechanistically, the preservations of mitochondrial function and VEGF expression were dependent on tetrameric structure and enzymatic activities of PKM2 in podocyte. These findings demonstrated that PKM2 structure and enzymatic activation in podocytes can preserve entire glomerular mitochondrial function against toxicity of hyperglycemia via paracrine factors such as VEGF and prevent DN progression.

DOI： 10.1172/jci.insight.155260

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/JPER.18-0735.

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.bbrc.2016.06.049.

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s13098-015-0047-y

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1152/ajpendo.00553.2014

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1074/jbc.M113.485730

Publisher：Frontiers Media SA  

Drug-induced gingival overgrowth (DIGO), induced by certain immunosuppressive drugs, antihypertensive agents, and antiepileptic drugs, may contribute to the formation of deeper periodontal pockets and intractableness in periodontitis. To date, multiple factors such as enhanced matrix production, inflammation, and reduced matrix degradation might be involved in the pathogenesis of DIGO. We have previously reported that SPOCK-1, a heparan sulfate proteoglycan, could affect gingival thickening by promoting epithelial-to-mesenchymal transition (EMT) in gingival keratinocytes. However, few studies have investigated whether a combination of these factors enhances the DIGO phenotype in animal models. Therefore, we investigated whether SPOCK-1, periodontal inflammation, and cyclosporin-A (CsA) could cooperatively promote gingival overgrowth. We first confirmed that Spock-1 overexpressing (Spock1-Tg) mice showed significantly thicker gingiva and greater alveolar bone loss than WT mice in response to ligature-induced experimental periodontitis. DIGO was induced by the combination of CsA administration and experimental periodontitis was significantly enhanced in Spock1-Tg mice compared to that in WT mice. Ligature-induced alveolar bone loss in CsA-treated Spock1-Tg mice was also significantly greater than that in CsA-treated WT mice, while being accompanied by an increase in Rankl and Col1a1 levels and a reduction in matrix metalloprotease expression. Lastly, SPOCK-1 promoted RANKL-induced osteoclast differentiation in both human peripheral blood mononuclear cells and murine macrophages, while peritoneal macrophages from Spock1-Tg mice showed less TNFα and IL-1β secretion than WT mice in response to Escherichia coli lipopolysaccharide. These results suggest that EMT, periodontal inflammation, and subsequent enhanced collagen production and reduced proteinase production contribute to CsA-induced DIGO pathogenesis.

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Language：Japanese   Publisher：(NPO)日本歯科保存学会  

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Language：Japanese   Publisher：(NPO)日本歯科保存学会  

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Language：Japanese   Publisher：(NPO)日本歯科保存学会  

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Language：Japanese   Publisher：(NPO)日本歯周病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Archives of Biochemistry and Biophysics  

A well-tuned inflammatory response is crucial for an effective immune process. Nuclear factor-kappa B (NF-κB) is a key mediator of inflammatory and innate immunity responses, and its dysregulation is closely associated with immune-related diseases. MicroRNAs (miRNAs) are important inflammation modulators. However, miRNA-regulated mechanisms that implicate NF-κB activity are not fully understood. This study aimed to identify a potential miRNA that could modulate the dysregulated NF-κB signaling during inflammation. We identified miR-582-5p that was significantly downregulated in inflamed murine adipose tissues and RAW264.7 cells. S-phase kinase-associated protein 1 (SKP1), a core component of an E3 ubiquitin ligase that regulates the NF-κB pathway, was proposed as a biological target of miR-582-5p by using TargetScan. The binding of miR-582-5p to a 3'-untranslated region site on Skp1 was confirmed using a dual-luciferase reporter assay; in addition, transfection with a miR-582-5p mimic suppressed SKP1 expression in RAW264.7 cells. Importantly, exogenous miR-582-5p attenuated the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 through suppressing the degradation of the NF-κB inhibitor alpha, followed by the nuclear translocation of NF-κB. Therefore, exogenously applied miR-582-5p can attenuate the NF-κB signaling pathway via targeting Skp1; this provides a prospective therapeutic strategy for treating inflammatory and immune diseases.

DOI： 10.1016/j.abb.2022.109501

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

The expression profiles of exosomal microRNAs (miRNAs) are regulated by the microenvironment, and appropriate priming with mesenchymal stem cells (MSCs) is one of the strategies to enhance the paracrine potency of MSCs. Our previous work demonstrated that exosomes from tumor necrosis factor (TNF)-α-primed human gingiva-derived MSCs (GMSCs) could be a therapeutic tool against periodontitis, and that TNFα-inducible exosomal miR-1260b is essential for the inhibition of alveolar bone loss. However, the precise molecular mechanism underlying miR-1260b-mediated inhibition of osteoclastogenesis is not yet fully understood. Here, we found that the activating transcription factor (ATF)-6β, a novel miR-1260b-targeting gene, is critical for the regulation of osteoclastogenesis under endoplasmic reticulum (ER) stress. An experimental periodontal mouse model demonstrated that induction of ER stress was accompanied by enhanced ATF6β expression, and local administration of miR-1260b and ATF6β siRNA using polyethylenimine nanoparticles (PEI-NPs) significantly suppressed the periodontal bone resorption. In periodontal ligament (PDL) cells, the ER stress inducer, tunicamycin, enhanced the expression of the receptor activator of NF-κB ligand (RANKL), while miR-1260b-mediated downregulation of ATF6β caused RANKL inhibition. Furthermore, the secretome from miR-1260b/ATF6β-axis-activated PDL cells inhibited osteoclastogenesis in human CD14^+ peripheral blood-derived monocytes. These results indicate that the miR-1260b/ATF6β axis mediates the regulation of ER stress, which may be used as a novel therapeutic strategy to treat periodontal disease.

DOI： 10.3389/fcell.2022.1061216

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Language：Japanese   Publisher：(NPO)日本歯科保存学会  

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Language：Japanese   Publisher：(NPO)日本歯周病学会  

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Language：Japanese   Publisher：(NPO)日本歯科保存学会  

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Language：Japanese   Publisher：(NPO)日本歯科保存学会  

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DOI： 10.1136/bmjdrc-2020-001871

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.actbio.2020.12.046.

Language：English   Publishing type：Research paper (scientific journal)  

SPOCK1 is a calcium-binding matricellular proteoglycan that has been extensively studied in several cancer cells. Previously, we generated a mouse line overexpressing SPOCK1 (Spock1-Tg mouse) and showed that SPOCK1 might play an important role in drug-induced gingival overgrowth, indicating that it possesses physiological functions in non-cancer diseases as well. Although SPOCK1 was reported to be secreted from human adipocytes, its role in adipocyte physiology has not been addressed yet. In this study, SPOCK1 protein expression was confirmed in pancreas, adipose tissues, spleen, and liver of normal diet (ND)-fed mice. Interestingly, SPOCK1 was up-regulated in the pancreas and adipose tissues of the high-fat diet (HFD)-fed mice. Spock1-Tg mice fed with ND showed increased maturation in epididymal and inguinal adipose tissues. In addition, Spock1 overexpression strongly decreased expression of UCP-1 in adipose tissues, suggesting that SPOCK1 might regulate thermogenic function through suppression of UCP-1 expression. Finally, exogenous SPOCK1 treatment directly accelerated the differentiation of 3T3-L1 adipocytes, accompanied by the up-regulation of adipocyte differentiation-related gene expression. In conclusion, we demonstrated for the first time that SPOCK1 induced adipocyte differentiation via the up-regulation of adipogenesis-related genes.

DOI： 10.1016/j.bbrc.2020.09.129

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

MicroRNA (miRNA) plays an important role in diverse cellular biological processes such as inflammatory response, differentiation and proliferation, and carcinogenesis. miR-146a has been suggested as a negative regulator of the inflammatory reaction. Although, it has been reported as expressed in inflamed adipose and periodontal tissues, however, miR-146a's inhibitory effects against inflammatory response in both the tissues, are not well understood. Therefore, in this study, the inhibitory effects of miR-146a on both adipose and periodontal inflammation, was investigated. In vitro study has revealed that miR-146a transfection into either adipocytes or gingival fibroblasts, has resulted in a reduced cytokine gene expression, observed on co-culturing the cells with macrophages in the presence of lipopolysaccharides (LPS), in comparison to the control miRNA transfected. Similarly, miR-146a transfection into macrophages resulted in a reduced expression of TNF-α gene and protein in response to LPS stimulation. In vivo study revealed that a continuous intravenous miR-146a administration into mice via tail vein, protected the mice from developing high-fat diet-induced obesity and the inflammatory cytokine gene expression was down-regulated in both adipose and periodontal tissues. miR-146a appeared to be induced by macrophage-derived inflammatory signals such as TNF-α by negative feed-back mechanism, and it suppressed inflammatory reaction in both adipose and periodontal tissues. Therefore, miR-146a could be suggested as a potential therapeutic molecule and as a common inflammatory regulator for both obesity-induced diabetes and related periodontal diseases.

DOI： 10.1016/j.bbrep.2020.100757

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DOI： 10.3389/fimmu.2020.00709

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DOI： 10.2337/dc18-2585.

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DOI： 10.1016/j.metabol.2017.01.006.

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DOI： 10.1016/j.numecd.2016.11.008

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DOI： 10.1055/s-0043-121467

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DOI： 10.1161/ATVBAHA.117.310291.

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DOI： 10.1016/j.bbrc.2017.11.069.

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DOI： 10.1002/oby.21127.

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Event date： 2019.11

Language：English   Presentation type：Oral presentation (general)  

Venue：Chicago   Country：United States  

Event date： 2019.10

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Venue：西日本国際展示場・北九州国際展示場   Country：Japan  

【背景】歯周病は糖尿病の第6の合併症として広く認知され高血糖が歯周炎の増悪に関わることが示唆されているが、肥満が糖尿病と独立して歯周炎の重症化に関わる可能性も指摘されている。近年の報告より、肥満・糖尿病ラットでは歯肉においてもインスリン抵抗性が惹起することが明らかとなっている。そこで、組織特異的インスリン受容体(IR)欠損マウスを用いて、歯周組織局所のインスリン抵抗性が肥満・糖尿病関連性歯周炎に及ぼす影響を検討することとした。【方法】血管平滑筋マーカーSM22αプロモーター下Cre発現マウスとIR-floxedマウスを交配し、血管平滑筋特異的IR欠損(SMIRKO)マウスを得た。また同腹仔野生型(WT)に通常食(RD)および高脂肪食負荷(HFD)を10週間行った。14週齢の各雄性マウスの第2臼歯に7-0絹糸を結紮し、実験的歯周炎を惹起した。【結果】WT(RD)と比較して、歯肉中IR発現はSMIRKOマウスで約70%、HFDマウスで約50%低下しており、両マウス歯肉ともインスリン誘導性Aktリン酸化の有意な抑制が見られ、さらに実験的歯周炎惹起後14日目では歯肉のTNFα、IL-1β、IL-17といった炎症性サイトカイン発現、歯槽骨吸収および破骨細胞形成が有意に上昇・亢進した。興味深いことに、SMIRKO・HFDマウスでは実験的歯周炎惹起後4日目の歯肉中の好中球数はWT(RD)マウスより有意に少なかったが、14日目では増加していた。【考察】歯肉におけるインスリン抵抗性は、歯周感染に対する好中球浸潤の遅延を起こし炎症反応が遷延化することで、歯周炎増悪に寄与することが示唆された。

Event date： 2019.10

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Venue：Seoul   Country：Korea, Republic of  

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Venue：Pennsilvania University, America   Country：United States  

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Venue：都市センターホテル、東京   Country：Japan  

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Venue：大阪国際会議場、大阪   Country：Japan  

Event date： 2024.11

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An emerging mechanism in diabetes-related periodontitis: the pathogenic role of insulin resistance in periodontal tissue

Event date： 2023.11

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Event date： 2023.10

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A novel pathological basis of diabetes-related periodontitis~ from the viewpoint of insulin resistance

Event date： 2023.10

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Award Lecture for Kyushu University Dental Science Best Research Award

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Event date： 2021.5

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Venue：オンライン   Country：Japan  

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Language：Japanese  

Language：Japanese   Publisher：(株)医学出版  

歯周病は,微小環境下(歯周ポケット内)に堆積したプラーク内で増加する,歯周病原細菌(グラム陰性嫌気性菌)感染を始まりとし,歯周病原細菌による歯周組織内への侵入に対する宿主の免疫応答によって誘導される炎症(dysbiotic inflammation)を本態とする点が歯周病の特徴である.糖尿病は宿主側の免疫細胞や歯周組織構成細胞の生理機能,口腔内細菌組成に変化をもたらしたり,全身性の慢性炎症状態を惹起したりするなど,歯周炎病態に多大な影響を及ぼすことが知られている.実際に糖尿病患者では歯周病罹患率が高く,重症化しやすいため,糖尿病で歯周病が進行・増悪するメカニズムを理解することは,非常に重要である.一方で,多くの糖尿病合併症においては,インスリン抵抗性がそれらの病態基盤に重要な役割を果たしていることが明らかとなってきている.そこで本稿では,インスリン抵抗性が糖尿病関連歯周炎の病態形成に寄与する役割について焦点を当て,最新の知見を交えながら解説したい.(著者抄録)

Language：Japanese   Publisher：(有)科学評論社