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Yamaaki, Naoto ; Yagi, Kunimasa ; Kobayashi, Junji ; Nohara, Atsushi ; Ito, Naoko ; Asano, Akimichi ; Nakano, Kaoru ; Liu, Jianhui ; Okamoto, Takuya ; Mori, Yukiko ; Ohbatake, Azusa ; Okazaki, Satoko ; Takeda, Yoshiyu ; Yamagishi, Masakazu
出版情報: Journal of Diabetes Research.  2013  pp.143515-,  2013-07-01.  Hindawi Publishing Corporation
URL: http://hdl.handle.net/2297/48398
概要: Background. Although retinol-binding protein 4 (RBP4) associates with insulin resistance and remnant-like particles trig lyceride (RLP-TG) elevated in the insulin resistant state, few data exist regarding the relationship between RBP4 and RLP-TG. Subjects and Methods. The study included 92 Japanese type 2 diabetic mellitus (T2DM) male patients (age 60.5 ± 13.6 years, body mass index (BMI) 24.7 ± 4.1 kg/m2, waist circumference (WC) 88.4 ± 10.7 cm, and HbA1c (NGSP) 7.2 ± 1.9 %). Patients on medications affecting insulin sensitivity, including fibrates, biguanides, and thiazolidinedione, were excluded. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by computed tomography. Results. RBP4 levels showed a significant positive correlation with RLP-TG (r = 0.2544 and P = 0.0056), TG (r = 0.1852 and P = 0.041), RLP-TG/TG (r = 0.23765 and P = 0.0241), and age (r = - 0.2082 and P = 0.0219), although there was no significant correlation with VFA, SFA, adiponectin levels, or homeostasis model of assessment insulin resistance (HOMA-R). Multiple regression analysis revealed that RBP4 was an independent determinant of RLP-TG (P = 0.0193) but was not a determinant of TG. Conclusions. RBP4 correlates positively with serum RLP-TG independent of fat accumulation in T2DM. RBP4 may regulate remnant metabolism independent of glycemic control in T2DM. © 2013 Naoto Yamaaki et al. 続きを見る
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Moriuchi, Tadashi ; Oka, Rie ; Yagi, Kunimasa ; Miyamoto, Susumu ; Nomura, Hideki ; Yamagishi, Masakazu ; Mabuchi, Hiroshi ; Kobayashi, Junji ; Koizumi, Junji
出版情報: Internal Medicine.  49  pp.1271-1276,  2010-07-01.  Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/28981
概要: Objective High-normal, the intermediate category between normal fasting glucose (NFG) and impaired fasting glucose (IFG) , was introduced in the criteria of the disordered glucose metabolism in 2008. The aim of this study was to investigate the risk for future incidence of type 2 diabetes of the subjects with high-normal and to examine how other metabolic variables could be useful for their risk stratification. Methods A historical cohort study was conducted from 2001 to 2008, inclusive, in 4,165 non-diabetic employees at public schools (2,229 men and 1,936 women; age 45.8±5.9 years, range 25-55 years). They were classified at baseline as NFG with fasting plasma glucose (FPG)<100 mg/dL, high-normal with FPG 100-109 mg/dL, and IFG with FPG 110-125 mg/dL. The incidence of type 2 diabetes (defined either by FPG 126 mg/dL or by receiving treatments) was measured. Results The cumulative incidence during a mean follow-up of 5.1 years were 16/3,364 (0.5%), 40/613 (6.5%), and 53/188 (28.2%) in subjects with NFG, high-normal, and IFG, respectively. Multivariate-adjusted odds ratios for the incidence were still significant both in high-normal and IFG compared to NFG. Body mass index (BMI) and alanine aminotransaminase (ALT) were associated with the incidence of type 2 diabetes independently of FPG categories (p<0.05). Conclusion The future incidence of type 2 diabetes in subjects with high-normal was significantly higher than in those with NFG in this population. BMI and ALT can improve risk stratification in high-normal subjects. © 2010 The Japanese Society of Internal Medicine. 続きを見る
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Imamura, S. ; Kobayashi, Junji ; Sakasegawa, S. ; Nohara, Atsushi ; Nakajima, Kenichi ; Kawashiri, Masa-aki ; Inazu, Akihiro ; Yamagishi, Masakazu ; Koizumi, Junji ; Mabuchi, Hiroshi ; 小林, 淳二 ; 野原, 淳 ; 中嶋, 憲一 ; 川尻, 剛照 ; 稲津, 明広 ; 山岸, 正和 ; 小泉, 順二 ; 馬渕, 宏
出版情報: Journal of Lipid Research.  48  pp.453-457,  2007-02.  American Society for Biochemistry and Molecular Biology
URL: http://hdl.handle.net/2297/00050262
概要: 金沢大学医薬保健研究域医学系<br />The objective of this study was to establish a hepatic lipase (HL) assay method that can be applied to automatic clinical analyzers. Seventy-four hyperlipidemic subjects (men/women 45/29) were recruited. Lipase activity was assayed measuring the increase in absorbance at 546 nm due to quinonediimine dye production. Reaction mixture R-1 contained 50 mM Tris-HCl (pH 9.5), 0.5 mM glycerol-1,2-dioleate, 0.4% (unless otherwise noted) polyoxyethylenenonylphenylether, 3 mM ATP, 3 mM MgCl2, 1.5 mM CaCl2, monoacylglycerol-specific lipase, glycerol kinase, glycerol-3-phosphate oxidase, 0.075% N,N-bis-(4-sulfobutyl)-3-methylaniline-2 Na, peroxidase, ascorbic acid oxidase. Reaction mixture R-2 contained 50 mM Tris-HCl (pH9.5), 0.15% 4-aminoantypirine. Automated assay for activity was performed with a Model 7080 Hitachi analyzer. In the lipase assay, 160 μl of R-1 was incubated at 37°C with 3 μl of samples for 5 min, and 80 μl of R-2 was added. Within-run coefficient of variations was 0.9-1.0%. Calibration curve of lipase activity was linear (r = 0.999) between 0 and 320 U/l. Analytical recoveries of purified HL added to plasma were 96.6-99.8%. HL activity in postheparin plasma measured in this method had a closer correlation with HL mass by a sandwich ELISA (r = 0.888, P , 0.0001) than those in the conventional method using [ 14C-]triolein (r = 0.730, P < 0.0001). This assay method for HL activity can be applied to an automatic clinical analyzer. Copyright © 2007 by the American Society for Biochemistry and Molecular Biology, Inc. 続きを見る
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Noguchi, Tohru ; Kobayashi, Junji ; Yagi, Kunimasa ; Nohara, Atsushi ; Yamaaki, Naoto ; Sugihara, Masako ; Ito, Naoko ; Oka, Rie ; Kawashiri, Masaaki ; Tada, Hayato ; Takata, Mutsuko ; Inazu, Akihiro ; Yamagishi, Masakazu ; Mabuchi, Hiroshi
出版情報: Atherosclerosis 217 (1), pp. 165-170.  217  pp.165-170,  2011-07-01.  Elsevier Ireland Ltd
URL: http://hdl.handle.net/2297/27306
概要: 金沢大学医学系研究科<br />Background: Bezafibrate and fenofibrate show different binding properties against peroxisome proliferato r-activated receptor subtypes, which could cause different clinical effects on circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and on various metabolic markers. Methods: An open, randomized, four-phased crossover study using 400 mg of bezafibrate or 200 mg of fenofibrate was performed. Study subjects were 14 dyslipidemia with impaired glucose tolerance or type 2 diabetes mellitus (61 ± 16 years, body mass index (BMI) 26 ± 3 kg/m2, total cholesterol (TC) 219 ± 53 mg/dL, triglyceride (TG) 183 ± 83 mg/dL, high-density lipoprotein-cholesterol (HDL-C) 46 ± 8 mg/dL, fasting plasma glucose 133 ± 31 mg/dL and HbA1c 6.2 ± 0.8%). Subjects were given either bezafibrate or fenofibrate for 8 weeks, discontinued for 4 weeks and then switched to the other fibrate for 8 weeks. Circulating PCSK9 levels and other metabolic parameters, including adiponectin, leptin and urine 8-hydroxy-2′-deoxyguanosine (8-OHdG) were measured at 0, 8, 12 and 20 weeks. Results: Plasma PCSK9 concentrations were significantly increased (+39.7% for bezafibrate and +66.8% for fenofibrate, p < 0.001) in all patients except for one subject when treated with bezafibrate. Both bezafibrate and fenofibrate caused reductions in TG (-38.3%, p < 0.001 vs. -32.9%, p < 0.01) and increases in HDL-C (+18.0%, p < 0.001 vs. +11.7%, p < 0.001). Fenofibrate significantly reduced serum cholesterol levels (TC, -11.2%, p < 0.01; non-HDL-C, -17.3%, p < 0.01; apolipoprotein B, -15.1%, p < 0.01), whereas bezafibrate significantly improved glucose tolerance (insulin, -17.0%, p < 0.05) and metabolic markers (γ-GTP, -38.9%, p < 0.01; adiponectin, +15.4%, p < 0.05; urine 8-OHdG/Cre, -9.5%, p < 0.05). Conclusion: Both bezafibrate and fenofibrate increased plasma PCSK9 concentrations. The addition of a PCSK9 inhibitor to each fibrate therapy may achieve beneficial cholesterol lowering along with desirable effects of respective fibrates. © 2011 Elsevier Ireland Ltd. All rights reserved. 続きを見る
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Tada, Hayato ; Kobayashi, Junji ; Kawashiri, Masa-aki ; Miyashita, Kazuya ; Nohara, Atsushi ; Inazu, Akihiro ; Nakajima, Katsuyuki ; Mabuchi, Hiroshi ; Yamagishi, Masakazu
出版情報: Lipids in Health and Disease.  15  pp.66-,  2016-04-02.  BioMed Central
URL: http://hdl.handle.net/2297/48355
概要: Background: This study was performed to compare the effects of three different lipid-lowering therapies (statins, ezetim ibe, and colestimide) on lipoprotein lipase and endothelial lipase masses in pre-heparin plasma (pre-heparin LPL and EL mass, respectively) from patients with familial hypercholesterolemia (FH). FH is usually treated by coadministration of these three drugs. Methods: The pre-heparin LPL and EL masses were measured in fresh frozen plasma drawn and stored at various time points during coadministration of the three drugs from patients with heterozygous FH harboring a single mutation in the LDL receptor (n = 16, mean age 63 years). The patients were randomly divided into two groups based on the timing when ezetimibe was added. Results: Plasma LPL mass concentration was significantly reduced by rosuvastatin at 20 mg/day (median = 87.4 [IQR: 71.4-124.7] to 67.5 [IQR: 62.1-114.3] ng/ml, P < 0.05). In contrast, ezetimibe at 10 mg/day as well as colestimide at 3.62 g/day did not alter its level substantially (median = 67.5 [IQR: 62.1-114.3] to 70.2 [IQR: 58.3-106.2], and to 74.9 [IQR: 55.6-101.3] ng/ml, respectively) in the group starting with rosuvastatin followed by the addition of ezetimibe and colestimide. On the other hand, the magnitude in LPL mass reduction was lower in the group starting with ezetimibe at 10 mg/day before reaching the maximum dose of 20 mg/day of rosuvastatin. Plasma EL mass concentration was significantly increased by rosuvastatin at 20 mg/day (median = 278.8 [IQR: 186.7-288.7] to 297.0 [IQR: 266.2-300.2] ng/ml, P < 0.05), whereas other drugs did not significantly alter its level. Conclusion: The effects on changes of LPL and EL mass differed depending on the lipid-lowering therapy, which may impact the prevention of atherosclerosis differently. © 2016 Tada et al. 続きを見る
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Kobayashi, Junji ; Murase, Yuko ; Asano, Akimichi ; Nohara, Atsushi ; Kawashiri, Masa-aki ; Inazu, Akihiro ; Yamagishi, Masakazu ; Mabuchi, Hiroshi ; 小林, 淳二 ; 野原, 淳 ; 川尻, 剛照 ; 稲津, 明広 ; 山岸, 正和 ; 馬渕, 宏
出版情報: Journal of Atherosclerosis and Thrombosis.  13  pp.197-201,  2006-08-15.  Japan Atherosclerosis Society = 日本動脈硬化学会
URL: http://hdl.handle.net/2297/48531
概要: Objective: To clarify the effects of walking with a pedometer on metabolic parameters, including adiponectin (APN). Meth ods: We recruited 44 male Japanese volunteers (age, 37 ± 9 yrs; body mass index (BMI), 24.2 ± 2.9 kg/m2; fasting plasma glucose (FPG), 96 ± 11 mg/dL; total cholesterol (TC) 190 ± 26 mg/dL; triglycerides (TG) 119 ± 80 mg/dL; HDL-C56 ± 14 mg/dL). Subjects were instructed to walk with a pedometer and record the number of steps they walked every day for 50 days. Serum adiponectin (APN) levels were measured by enzyme immunoassay. Treatment effects were examined by Wilcoxon's rank test. Results: The average number of steps was 8211 ± 2084 per day. There were significant reductions in BMI, sBP, TG and TNF-α levels after 50 days, but no changes in adiponectin levels. We then divided the subjects into 2 groups according to the steps walked per day, namely, more than 8000 steps (MT group, n=22) and less than 8000 steps (LT group, n=22) and found that the reduction in TG and BP was observed only in the MT group. Conclusions: Walking with a pedometer is effective for improving metabolic parameters, such as TG and blood pressure, but is not sufficient to increase adiponectin levels in Japanese men.<br />出版者照会後に全文公開 続きを見る
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Nozue, Tsuyoshi ; Higashikata, Toshinori ; Inazu, Akihiro ; Kawashiri, Masa-aki ; Nohara, Atsushi ; Kobayashi, Junji ; Koizumi, Junji ; Yamagishi, Masakazu ; Mabuchi, Hiroshi
出版情報: Internal Medicine.  49  pp.1127-1131,  2010-06-01.  Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/48447
概要: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive sterol storage disease caused by a mutated sterol 27- hydroxylase (CYP27A1) gene. We analyzed the CYP27A1 gene in two Japanese CTX patients. The CYP27A1 gene was amplified by PCR and screened by PCR-SSCP. The nucleotide sequence was analyzed to confirm mutations. Case 1 was a compound heterozygote for Arg104Gln in exon 2 and Arg441Gln in exon 8. To our knowledge, this is the first report in which the Arg104Gln mutation is identified in CTX patients. Probably case 2 would be a compound heterozygote for Arg441Trp in exon 8 and a mutation that was not identified. © 2010 The Japanese Society of Internal Medicine. 続きを見る
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Tada, Hayato ; Kawashiri, Masaaki ; Noguchi, Tohru ; Mori, Mika ; Tsuchida, Masayuki ; Takata, Mutsuko ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Yachie, Akihiro ; Mabuchi, Hiroshi ; Yamagishi, Masakazu
出版情報: Clinica Chimica Acta.  400  pp.42-47,  2009-02-01.  Elsevier
URL: http://hdl.handle.net/2297/14392
概要: 金沢大学附属病院循環器内科<br />Background: The objective of this study was to develop a new and simple method for measuring low-dens ity lipoprotein receptor (LDLR) activity using peripheral lymphocytes enabling us to clinically diagnose familial hypercholesterolemia (FH) and ascertain the involved mutations (such as K790X mutation), that might not be clearly detected in the conventional method. Methods: Our method comprised the following 2 features: first, we used anti-CD3/CD28 beads to stimulate T-lymphocytes to obtain a uniform fraction of lymphocytes and maximum up-regulation of LDLR. Second, we excluded the possibility of overestimation of lymphocyte signals bound only to its surface, by adding heparin to the cultured lymphocytes used for the LDLR assay. Results: Based on the genetic mutation, the FH subjects were divided into 2 groups, K790X, (n = 20) and P664L, (n = 5), and their LDLR activities was measured by this method, which was found to be 55.3 ± 8.9% and 63.9 ± 13.8%, respectively, of that of the control group (n = 15). In comparison, the LDLR activity was 86.1 ± 11.6% (K790X) and 73.3 ± 6.3% (P664L) of that of the control group when measured by the conventional method, indicating that impairment of LDLR function in FH K790X subjects was much more clearly differentiated with our method than with the conventional method (paired t-test, p < 0.0001). The levels of LDLR expression also showed similar tendencies, that is, 89.4 ± 13.2% (K790X) and 76.9 ± 17.4% (P664L) of that of the control group when measured by the conventional method, and 78.1 ± 9.7% (K790X) and 70.3 ± 26.5% (P664L) when measured by our new method. In addition, we confirmed that there was little influence of statin treatment on LDLR activity among the study subjects when our method was used. Conclusion: These results demonstrate that our new method is applicable for measuring LDLR activity, even in subjects with an internally defective allele, and that T-lymphocytes of the FH K790X mutation possess characteristics of that allele. © 2008 Elsevier B.V. All rights reserved. 続きを見る
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Ohtsuji, Michio ; Yagi, Kunimasa ; Shintaku-Kubota, Miyuki ; Kojima-Koba, Yukiko ; Ito, Naoko ; Sugihara, Masako ; Yamaaki, Naoto ; Chujo, Daisuke ; Nohara, Atsushi ; Takeda, Yoshiyu ; Kobayashi, Junji ; Yamagishi, Masakazu ; Higashida, Haruhiro
出版情報: Experimental diabetes research.  2008  pp.89758-,  2008-12-01.  Hindawi Publishing Corporation
URL: http://hdl.handle.net/2297/18975
概要: 金沢大学附属病院<br />AIMS/HYPOTHESIS: ADP-ribosyl-cyclase activity (ADPRCA) of CD38 and other ectoenzymes mainly generate cycli c adenosine 5'diphosphate-(ADP-) ribose (cADPR) as a second messenger in various mammalian cells, including pancreatic beta cells and peripheral blood mononuclear cells (PBMCs). Since PBMCs contribute to the pathogenesis of diabetic nephropathy, ADPRCA of PBMCs could serve as a clinical prognostic marker for diabetic nephropathy. This study aimed to investigate the connection between ADPRCA in PBMCs and diabetic complications. METHODS: PBMCs from 60 diabetic patients (10 for type 1 and 50 for type 2) and 15 nondiabetic controls were fluorometrically measured for ADPRCA based on the conversion of nicotinamide guanine dinucleotide (NGD(+)) into cyclic GDP-ribose. RESULTS: ADPRCA negatively correlated with the level of HbA1c (P = .040, R(2) = .073), although ADPRCA showed no significant correlation with gender, age, BMI, blood pressure, level of fasting plasma glucose and lipid levels, as well as type, duration, or medication of diabetes. Interestingly, patients with nephropathy, but not other complications, presented significantly lower ADPRCA than those without nephropathy (P = .0198) and diabetes (P = .0332). ANCOVA analysis adjusted for HbA1c showed no significant correlation between ADPRCA and nephropathy. However, logistic regression analyses revealed that determinants for nephropathy were systolic blood pressure and ADPRCA, not HbA1c. CONCLUSION/INTERPRETATION: Decreased ADPRCA significantly correlated with diabetic nephropathy. ADPRCA in PBMCs would be an important marker associated with diabetic nephropathy. 続きを見る
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Tada, Hayato ; Kawashiri, Masa-aki ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Yasuda, Kenji ; Mabuchi, Hiroshi ; Yamagishi, Masakazu ; Hayashi, Kenshi ; 多田, 隼人 ; 川尻, 剛照 ; 野原, 淳 ; 稲津, 明広 ; 小林, 淳二 ; 馬淵, 宏 ; 山岸, 正和 ; 林, 研至
出版情報: Journal of Atherosclerosis and Thrombosis.  24  pp.338-345,  2017.  日本動脈硬化学会 = Japan Atherosclerosis Society
URL: http://hdl.handle.net/2297/00053012
概要: 金沢大学附属病院循環器内科<br />Aim: The Japan Atherosclerosis Society (JAS) guidelines for the prevention of atherosclerotic disease s 2012 (JAS2012) proposed lipid management targets; however, less data is available regarding the attainment rates of each target in community-based settings. Therefore, we assessed the attainment rates of lipid management targets among subjects who underwent Japanese specific health checkups.\nMethods: A total of 85,716 subjects (male=29,282, 34.2%) aged 40–74 years who underwent specific health checkups from 2012 to 2014 in Kanazawa city, Japan, were included in this study. We evaluated the attainment rates of the lipid management targets according to the JAS2012 guideline and investigated the clinical characteristics of the subjects without achieving the targets.\nResults: The target for LDL cholesterol (LDL-C) was the least attained in all risk categories, 89, 72, 50, and 34% for category I, II, III, and secondary prevention, respectively, in 2014. In addition, these rates inversely correlated with the grade of risk categories (p-value for trends <0.001). Attainment rate of the LDL-C target in the suspected chronic kidney disease (CKD) group was significantly lower than in the groups with diabetes, stroke, or absolute risk in category III (49.2, 60.3, 63.5, 54.4%, respectively, p-value <0.001 for each). Moreover, the attainment rate of the LDL-C target was significantly lower in subjects that did not receive lipid-lowering therapy than in those who received it in the secondary prevention (27.7 and 40.6%, respectively, p-value <0.001).\nConclusions: Lipid management is inadequate in community-based settings, particularly, in subjects with CKD and secondary prevention.<br />This article distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License. 続きを見る