Papers - TANNO Masaya

AKIに対するアンジオテンシンII前投与による腎保護効果はAT1およびMas受容体減少の軽減とautophagy活性化を伴う

菅原 浩仁, 茂庭 仁人, 柴田 智, 矢野 俊之, 久野 篤史, 丹野 雅也, 三木 隆幸, 三浦 哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 )  61 ( 3 ) 285 - 285  2019.05

Accuracy of flash glucose monitoring in insulin-treated patients with type 2 diabetes.

Tatsuya Sato, Hiroto Oshima, Kei Nakata, Yukishige Kimura, Toshiyuki Yano, Masato Furuhashi, Masaya Tanno, Takayuki Miki, Tetsuji Miura

Journal of diabetes investigation   10 ( 3 ) 846 - 850  2019.05  [Refereed]  [Domestic journal]

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The present study evaluated the accuracy of interstitial glucose measurements by flash glucose monitoring (FGM) and continuous glucose monitoring (CGM). Five diabetes patients simultaneously underwent FGM (FreeStyle Libre Pro) and CGM (iPro™2), and their glucose levels were compared with venous blood and capillary blood glucose levels. The range of daily venous blood glucose levels (30 measurements) was 70-245 mg/dL, with a median of 138 mg/dL. There were good correlations of glucose levels measured by FGM (r2  = 0.90, mean absolute relative difference 8.2 ± 5.6%), CGM (r2  = 0.86, mean absolute relative difference 9.2 ± 9.1%) and capillary blood (r2  = 0.87, mean absolute relative difference 7.2 ± 7.2%) with venous blood glucose levels. The accuracy of FGM measurements was also shown against CGM, with 99.9% of the FGM values (1,279 measurements) being within the Parkes error grid zones A and B. The results suggest that the accuracy of FGM is similar to that of CGM, and that FGM is a useful tool for determining daily glucose profile.

DOI PubMed

糖尿病の外来診療における慢性合併症評価実態の検討

伊野 祥哉, 中田 圭, 東浦 幸村, 佐藤 達也, 矢野 俊之, 古橋 眞人, 丹野 雅也, 三木 隆幸, 斎藤 重幸, 三浦 哲嗣

糖尿病 ( (一社)日本糖尿病学会 )  62 ( Suppl.1 ) S - 306  2019.04

Empagliflozin, an SGLT2 inhibitor, reduced the mortality rate after acute myocardial infarction with modification of cardiac metabolomes and anti-oxidants in diabetic rats.

Oshima H, Miki T, Kuno A, Mizuno M, Sato T, Tanno M, Yano T, Nakata K, Kimura Y, Abe K, Ohwada W, Miura T

The Journal of pharmacology and experimental therapeutics   368 ( 3 ) 524 - 534  2019.03  [Refereed]

DOI PubMed

エピジェネティクスにおけるNon-coding RNA 糖尿病性心筋症の重要因子であるAMP deaminaseの新規microRNA介在性制御(Non-coding RNAs as Regulators in Epigenetics Novel microRNA-mediated Regulation of AMP Deaminase, a Key Player in Diabetic Cardiomyopathy)

Tanno Masaya, Tatekoshi Yuki, Kouzu Hidemichi, Kuno Atsushi, Yano Toshiyuki, Miki Takayuki, Miura Tetsuji

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  83回   SY14 - 4  2019.03

JDS-JCSジョイントシンポ(Controversy or Debate)-"Stop DM for Stop CVD"生命予後改善のための糖尿病管理とは 心血管イベントリスクの高い糖尿病患者を検出するためのECG検査の重要性とSGLT2阻害薬によって得られる利点(Importance of ECG Examination to Detect High Risk Diabetic Patients for Cardiovascular Events and Their Benefit Afforded by SGLT2 Inhibitors)

三木 隆幸, 佐藤 達也, 大西 浩文, 矢野 俊之, 中田 圭, 丹野 雅也, 三浦 哲嗣

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  83回   SY12 - 3  2019.03

バソプレシンV2受容体機能が維持された心不全患者において、トルバプタンの早期開始は長期予後を改善する

能登 貴弘, 丹野 雅也, 永野 伸卓, 長南 新太, 神津 英至, 三浦 哲嗣

日本内科学会雑誌 ( (一社)日本内科学会 )  108 ( Suppl. ) 265 - 265  2019.02

【心不全(第2版)上-最新の基礎・臨床研究の進歩-】心不全の基礎研究 心不全の分子機序 心筋リモデリング DNA・転写制御障害 Sirtuin

丹野 雅也, 久野 篤史

日本臨床 ( (株)日本臨床社 )  76 ( 増刊9 心不全(上) ) 325 - 330  2018.12

Does p53 Inhibition Suppress Myocardial Ischemia-Reperfusion Injury?

Yano T, Abe K, Tanno M, Miki T, Kuno A, Miura T, Steenbergen C

Journal of cardiovascular pharmacology and therapeutics   23 ( 4 ) 350 - 357  2018.07  [Refereed]

DOI PubMed

Empagliflozin normalizes the size and number of mitochondria and prevents reduction in mitochondrial size after myocardial infarction in diabetic hearts.

Mizuno M, Kuno A, Yano T, Miki T, Oshima H, Sato T, Nakata K, Kimura Y, Tanno M, Miura T

Physiological Reports   6 ( 12 ) e13741  2018.06  [Refereed]

DOI PubMed

Translational regulation by miR-301b upregulates AMP deaminase in diabetic hearts.

Tatekoshi Y, Tanno M, Kouzu H, Abe K, Miki T, Kuno A, Yano T, Ishikawa S, Ohwada W, Sato T, Niinuma T, Suzuki H, Miura T

Journal of Molecular and Cellular Cardiology   119   138 - 146  2018.06  [Refereed]

DOI PubMed

糖尿病が重症急性心不全の予後に及ぼす影響

柴田 智, 三木 隆幸, 山下 智久, 菅原 浩仁, 佐藤 達也, 大島 洸人, 矢野 俊之, 丹野 雅也, 三浦 哲嗣

糖尿病 ( (一社)日本糖尿病学会 )  61 ( Suppl.1 ) S - 426  2018.04

アンジオテンシンIIの短期投与は尿細管autophagyを活性化し,急性腎障害を軽減する

菅原 浩仁, 茂庭 仁人, 柴田 智, 木村 幸滋, 山下 智久, 矢野 俊之, 久野 篤史, 丹野 雅也, 三木 隆幸, 三浦 哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 )  60 ( 3 ) 460 - 460  2018.04

Diabetes increases the susceptibility to acute kidney injury after myocardial infarction through augmented activation of renal Toll-like receptors in rats

Kouhei Ohno, Atsushi Kuno, Hiromichi Murase, Shingo Muratsubaki, Takayuki Miki, Masaya Tanno, Toshiyuki Yano, Satoko Ishikawa, Tomohisa Yamashita, Tetsuji Miura

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY ( AMER PHYSIOLOGICAL SOC )  313 ( 6 ) H1130 - H1142  2017.12  [Refereed]

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Acute kidney injury (AKI) after acute myocardial infarction (MI) worsens the prognosis of MI patients. Although type 2 diabetes mellitus (DM) is a major risk factor of AKI after MI, the underlying mechanism remains unclear. Here, we examined the roles of renal Toll-like receptors (TLRs) in the impact of DM on AKI after MI. MI was induced by coronary artery ligation in Otsuka-Long-Evans-Tokushima fatty (OLETF) rats, a rat DM model, and Long-Evans-Tokushima-Otsuka (LETO) rats, nondiabetic controls. Sham-operated rats served as no-MI controls. Renal mRNA levels of TLR2 and myeloid differentiation factor 88 (MyD88) were significantly higher in sham-operated OLETF rats than in sham-operated LETO rats, although levels of TLR1, TLR3, and TLR4 were similar. At 12 h after MI, protein levels of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in the kidney were elevated by 5.3-and 4.0-fold, respectively, and their mRNA levels were increased in OLETF but not LETO rats. The increased KIM-1 and NGAL expression levels after MI in the OLETF kidney were associated with upregulated expression of TLR1, TLR2, TLR4, MyD88, IL-6, TNF-alpha. chemokine (C-C motif) ligand 2. and transforming growth factor-beta(1) and also with activation of p38 MAPK, JNK, and NF-kappa B. Cu-CPT22, a TLR1/TLR2 antagonist, administered before MI significantly suppressed MI-induced upregulation of KIM-1, TLR2, TLR4, MyD88, and chemokine (C-C motif) ligand 2 levels and activation of NF-kappa B, whereas NGAL levels and IL-6 and TNF-alpha expression levels were unchanged. The results suggest that DM increases the susceptibility to AKI after acute MI by augmented activation of renal TLRs and that TLR1/TLR2-mediated signaling mediates KIM-1 upregulation after MI. NEW & NOTEWORTHY This is the first report to demonstrate the involvement of Toll-like recpetors (TLRs) in diabetes-induced susceptibility to acute kidney injury after acute myocardial infarction. We propose that the TLR1/TLR2 heterodimer may be a new therapeutic. target for the prevention of acute kidney injury in diabetic patients.

DOI PubMed

Distinct impacts of sleep-disordered breathing on glycemic variability in patients with and without diabetes mellitus

Kei Nakata, Takayuki Miki, Masaya Tanno, Hirofumi Ohnishi, Toshiyuki Yano, Atsuko Muranaka, Tatsuya Sato, Hiroto Oshima, Yuki Tatekoshi, Masashi Mizuno, Koki Abe, Tetsuji Miura

PLOS ONE ( PUBLIC LIBRARY SCIENCE )  12 ( 12 ) e0188689  2017.12  [Refereed]

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Background Sleep-disordered breathing (SDB) is highly prevalent in patients with diabetes mellitus (DM) and heart failure (HF) and contributes to poor cardiovascular outcomes. Enlarged glycemic variability (GV) is a risk factor of cardiac events independently of average blood glucose level, but the influence of SDB on GV is uncertain. In this study, we examined whether the impact of SDB on GV is modified by the presence of DM with or without HF. Methods and results Two hundred three patients (67.5 +/- 14.1 [ SD] years old, 132 males) who were admitted to our institute for examination or treatment of DM and/or HF underwent continuous glucose monitoring and polysomnography. Both HbA1c (8.0 +/- 2.0 vs. 5.7 +/- 0.4%) and mean amplitude of glycemic excursion (MAGE, median: 95.5 vs. 63.5 mg/dl) were significantly higher in a DM group (n = 100) than in a non-DM group (n = 103), but apnea-hypopnea index (AHI: 29.0 +/- 22.7 vs. 29.3 +/- 21.5) was similar in the two groups. AHI was correlated with log MAGE in the non-DM group but not in the DM group, and multivariate regression analysis revealed that AHI was an independent variable for log MAGE in the non-DM group but not in the DM group. We then divided the non-DM patients into two subgroups according to BNP level (100 pg/ml). AHI was positively correlated with log MAGE (r = 0.74, p<0.001) in the non-DM low-BNP subgroup, but such a correlation was not found in the non-DM high-BNP subgroup. Continuous positive airway pressure (CPAP) reduced MAGE from 75.3 to 53.0 mg/dl in the non-DM group but did not reduce MAGE in the DM group. Conclusion Severity of SDB was associated with higher GV, but DM as well as HF diminished the contribution of SDB to GV. Treatment with CPAP was effective for reduction of GV only in patients without DM.

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Effect of sodium-glucose co-transporter-2 inhibitors on impaired ventricular repolarization in people with Type 2 diabetes

T. Sato, T. Miki, H. Ohnishi, T. Yamashita, A. Takada, T. Yano, M. Tanno, A. Tsuchida, T. Miura

DIABETIC MEDICINE ( WILEY )  34 ( 10 ) 1367 - 1371  2017.10  [Refereed]

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AimsTo test the hypothesis that treatment with a sodium-glucose co-transporter-2 inhibitor would reverse ventricular repolarization heterogeneity, a predictor of cardiovascular mortality, in people with Type 2 diabetes. MethodsWe retrospectively analysed changes in indices of ventricular repolarization before and after treatment with a sodium-glucose co-transporter-2 inhibitor in 46 people with Type 2 diabetes. ResultsSodium-glucose co-transporter-2 inhibitor treatment reduced HbA(1c) concentration [6213 mmol/mol (7.71.2%) vs 5916 mmol/mol (7.51.4%)], body weight (77.8 +/- 13.9 vs 74.7 +/- 12.5 kg) and systolic blood pressure (133 +/- 18 vs 126 +/- 12 mmHg) in the study participants. Heart rate and QTc interval were not changed by sodium-glucose co-transporter-2 inhibitor treatment, but QTc dispersion was significantly reduced (median, 48.8 vs 44.2 ms). Sodium-glucose co-transporter-2 inhibitor treatment reversed QTc dispersion more in participants who had larger QTc dispersion before the treatment. Changes in systolic blood pressure (Spearman's = 0.319; P=0.031), but not in HbA(1c) concentration, were correlated with changes in QTc dispersion after sodium-glucose co-transporter-2 inhibitor treatment. ConclusionsThe findings suggest that sodium-glucose co-transporter-2 inhibitor treatment reverses ventricular repolarization heterogeneity in people with Type 2 diabetes, independently of its effect on glycaemic control. The favourable effect on ventricular repolarization heterogeneity could be the mechanism by which empaglifozin reduced cardiovascular events in a recent study.

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循環器内科学 心不全の発症進展におけるAMPデアミナーゼの役割

舘越 勇輝, 丹野 雅也

医学のあゆみ ( 医歯薬出版(株) )  262 ( 3 ) 243 - 244  2017.07

Suppression of autophagic flux contributes to cardiomyocyte death by activation of necroptotic pathways.

Ogasawara M, Yano T, Tanno M, Abe K, Ishikawa S, Miki T, Kuno A, Tobisawa T, Muratsubaki S, Ohno K, Tatekoshi Y, Nakata K, Ohwada W, Miura T

Journal of molecular and cellular cardiology   108   203 - 213  2017.07  [Refereed]

DOI PubMed

Suppressed autophagic response underlies augmentation of renal ischemia/reperfusion injury by type 2 diabetes

Shingo Muratsubaki, Atsushi Kuno, Masaya Tanno, Takayuki Miki, Toshiyuki Yano, Hirohito Sugawara, Satoru Shibata, Koki Abe, Satoko Ishikawa, Kouhei Ohno, Yukishige Kimura, Yuki Tatekoshi, Kei Nakata, Wataru Ohwada, Masashi Mizuno, Tetsuji Miura

SCIENTIFIC REPORTS ( NATURE PUBLISHING GROUP )  7 ( 1 ) 5311  2017.07  [Refereed]

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Diabetes mellitus is a major risk factor for acute kidney injury (AKI). Here, we hypothesized that suppression of autophagic response underlies aggravation of renal ischemia/reperfusion (I/R) injury by type 2 diabetes mellitus (T2DM). In OLETF, a rat model of T2DM, and its non-diabetic control, LETO, AKI was induced by unilateral nephrectomy and 30-min occlusion and 24-h reperfusion of the renal artery in the contralateral kidney. Levels of serum creatinine and blood urea nitrogen and tubular injury score after I/R were significantly higher in OLETF than in LETO. Administration of chloroquine, a widely used autophagy inhibitor, aggravated I/R-induced renal injury in LETO, but not in OLETF. In contrast to LETO, OLETF exhibited no increase in autophagosomes in the proximal tubules after I/R. Immunoblotting showed that I/R activated the AMPK/ULK1 pathway in LETO but not in OLETF, and mTORC1 activation after I/R was enhanced in OLETF. Treatment of OLETF with rapamycin, an mTORC1 inhibitor, partially restored autophagic activation in response to I/R and significantly attenuated I/R-induced renal injury. Collectively, these findings indicate that suppressed autophagic activation in proximal tubules by impaired AMPK/ULK1 signaling and upregulated mTORC1 activation underlies T2DM-induced worsening of renal I/R injury.

DOI PubMed

Insufficient activation of Akt upon reperfusion because of its novel modification by reduced PP2A-B55 alpha contributes to enlargement of infarct size by chronic kidney disease

Toshiyuki Tobisawa, Toshiyuki Yano, Masaya Tanno, Takayuki Miki, Atsushi Kuno, Yukishige Kimura, Satoko Ishikawa, Hidemichi Kouzu, Keitaro Nishizawa, Hideaki Yoshida, Tetsuji Miura

BASIC RESEARCH IN CARDIOLOGY ( SPRINGER HEIDELBERG )  112 ( 3 ) 31  2017.05  [Refereed]

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Chronic kidney disease (CKD) increases myocardial infarct size by an unknown mechanism. Here we examined the hypothesis that impairment of protective PI3K-PDK1-Akt and/or mTORC-Akt signaling upon reperfusion contributes to CKD-induced enlargement of infarct size. CKD was induced in rats by 5/6 nephrectomy (SNx group) 4 weeks before myocardial infarction experiments, and sham-operated rats served as controls (Sham group). Infarct size as a percentage of area at risk after ischemia/reperfusion was significantly larger in the SNx group than in the Sham group (56.3 +/- 4.6 vs. 41.4 +/- 2.0%). In SNx group, myocardial p-Akt-Thr308 level at baseline was elevated, and reperfusion-induced phosphorylation of p-Akt-Ser473, p-p70s6K and p-GSK-3 beta was significantly suppressed. Inhibition of Akt-Ser473 phosphorylation upon reperfusion by Ku-0063794 significantly increased infarct size in the Sham group but not in the SNx group. There was no difference between the two groups in activities of mTORC2 and PDK1 and protein level of PTEN. However, the PP2A regulatory subunit B55 alpha, which specifically targets Akt-Thr308, was reduced by 24% in the SNx group. Knockdown of B55 alpha by siRNA increased baseline p-Akt-Thr308 and blunted Akt-Ser473 phosphorylation in response to insulin-like growth factor-1 (IGF-1) in H9c2 cells. A blunted response of Akt-Ser473 to IGF-1 was also observed in HEK293 cells transfected with a p-Thr308-mimetic Akt mutant (T308D). These results indicate that increased Akt-Thr308 phosphorylation by down-regulation of B55 alpha inhibits Akt-Ser473 phosphorylation upon reperfusion in CKD and that the impaired Akt activation by insufficient Ser473 phosphorylation upon reperfusion contributes to infarct size enlargement by CKD.

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