Taka-Aki Matsuoka

The University of Tokushima, Tokusima, Tokushima, Japan

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Publications (114)418.72 Total impact

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    ABSTRACT: The aim of this study was to investigate the clinical and endocrinological characteristics of adrenal incidentalomas in Osaka region, Japan. The study was a multicenter retrospective analysis of 150 patients with adrenal incidentalomas who underwent radiographic and endocrine evaluations between 2005 and 2013. Most adrenal incidentalomas were discovered by computed tomography (77.0%) and the rest were identified by abdominal ultrasonography (14.6%), magnetic resonance imaging (4.2%), or positron emission tomography (4.2%). Adrenal incidentalomas were more frequently localized on the left side than on the right. The average diameter of tumors was 21 ± 11 mm. On endocrinological evaluation, 14 patients were diagnosed with primary aldosteronism (9.3%), 10 with subclinical Cushing's syndrome (6.7%), 7 with pheochromocytoma (4.7%), 7 with Cushing's syndrome (4.7%), 2 with both subclinical Cushing's syndrome and primary aldosteronism (1.3%), and 110 with non-functioning tumors (73.3%). Patients with functioning tumors were significantly younger and had larger tumor diameters than those with non-functioning tumors. Except for hypertension, complications were comparable between patients with functioning and non-functioning tumors, including the presence of glucose intolerance, cardiovascular disease, and dyslipidemia. In conclusion, a higher prevalence of primary aldosteronism was observed compared with a previous report. Complications were comparable between patients with functioning and non-functioning tumors, including the frequencies of glucose intolerance, cardiovascular disease, and dyslipidemia. Long-term follow-up is required in patients with non-functioning tumors because the frequency of complications, such as glucose intolerance, cardiovascular disease, and dyslipidemia, was equal to that in patients with functioning tumors.
    Endocrine Journal 10/2015; DOI:10.1507/endocrj.EJ15-0404 · 2.00 Impact Factor
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    ABSTRACT: Alleviation of hyperglycaemia and hyperlipidaemia improves pancreatic β-cell function in type 2 diabetes. However, the underlying molecular mechanisms are still not well clarified. In this study, we aimed to elucidate how the expression alterations of key β-cell factors is altered by the short-term selective alleviation of glucotoxicity or lipotoxicity. We treated db/db mice for one week with empagliflozin and/or bezafibrate to alleviate glucotoxicity and/or liptotoxicity, respectively. The gene expression levels of Pdx1 and Mafa, and their potential targets, insulin 1, Slc2a2, and Glp1r, were higher in the islets of empagliflozin-treated mice, and levels of insulin 2 were higher in mice treated with both reagents, than in untreated mice. Moreover, compared to the pretreatment levels, Mafa and insulin 1 expression increased in empagliflozin-treated mice, and Slc2a2 increased in combination-treated mice. In addition, empagliflozin treatment enhanced β-cell proliferation assessed by Ki-67 immunostaining. Our date clearly demonstrated that the one-week selective alleviation of glucotoxicity led to the better expression levels of the key β-cell factors critical for β-cell function over pretreatment levels, and that the alleviation of lipotoxicity along with glucotoxicity augmented the favourable effects under diabetic conditions.
    Biochemical and Biophysical Research Communications 10/2015; DOI:10.1016/j.bbrc.2015.10.038 · 2.30 Impact Factor
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    ABSTRACT: Lineage conversion of non-beta cells into insulin-producing cells has been proposed as a therapy for the cure of diabetes. Glucagon-like peptide-1 (GLP-1) and its derivatives can induce beta cell neogenesis in vitro and beta cell mass expansion in vivo, but GLP-1 signalling has not been shown to regulate cell fate decisions in vivo. We therefore tested the impact of GLP-1 receptor (GLP1R) expression on beta cell differentiation in vivo. Mice overexpressing GLP1R in pancreatic exocrine cells were generated by Cre-mediated recombination in sex-determining region Y-box 9 (SOX9)-expressing cells and then treated with exendin-4 and/or gastrin. Histological analysis was performed to detect cellular reprogramming from the exocrine lineage into insulin-producing cells. Whereas no newly generated beta cells were detected in the mice treated with exendin-4 alone, treatment with gastrin only induced the conversion of exocrine cells into insulin-producing cells. Furthermore, the overexpression of GLP1R, together with gastrin and exendin-4, synergistically promoted beta cell neogenesis accompanied by the formation of islet-like clusters. These newly generated beta cells expressed beta cell specific transcription factors, such as pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 (NKX6.1) and musculoaponeurotic fibrosarcoma oncogene family A (MafA). These mice showed no histological evidence of pancreatitis or pancreatic dysplasia in their acini and had normal plasma amylase levels. Activation of GLP-1 and gastrin signalling induces beta cell neogenesis in the exocrine lineage without any deleterious pancreatic changes, which may lead to a potential therapy to cure diabetes by generating surrogate beta cells.
    Diabetologia 08/2015; 58(11). DOI:10.1007/s00125-015-3728-z · 6.67 Impact Factor
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    ABSTRACT: Pancreatic β-cells secrete insulin when blood glucose levels become high, but when β-cells are chronically exposed to hyperglycemia, β-cells function gradually deteriorates which is known as β-cells glucose toxicity. In the diabetic state, nuclear expression levels of pancreatic transcription factors PDX-1 and MafA are decreased. In addition, incretin receptor expression in β-cellss is decreased, which is likely involved in the impairment of incretin effects in diabetes. In practical medicine, it is very important to select appropriate therapy for type 2 diabetes so that β-cells function can be preserved. In addition, when we start appropriate pharmacological intervention against β-cells glucose toxicity at an early stage of diabetes, β-cells function is substantially restored, which is not observed at an advanced stage. Taken together, it is likely that down-regulation of pancreatic transcription factors and/or incretin receptors are involved in β-cells dysfunction observed in type 2 diabetes and it is very important to start appropriate pharmacological intervention against β-cells glucose toxicity at an early stage of diabetes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Diabetes 07/2015; DOI:10.1111/1753-0407.12331 · 1.93 Impact Factor
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    ABSTRACT: We statistically investigated whether the impact of cardiovascular risk factors on arterial stiffness would be different from that on arterial wall thickness. We analyzed 1648 Japanese type 2 diabetic patients. Arterial stiffness was evaluated by pulse wave verbosity (PWV) and wall thickness was assessed with carotid intima-media thickness (IMT) by ultrasonography. We developed a common regression model to PWV and IMT by extending the linear mixed model and statistically detected the difference in the impact of cardiovascular risk factors between the two indices. There was a significant correlation between PWV and IMT (r=0.365, p<0.001). Sex, diabetic duration, hemoglobin A1c levels, and the presence of retinopathy and cardiovascular disease were comparable independent risk factors for elevated PWV and IMT. On the other hand, the impact of age, systolic blood pressure, and low- and high-density lipoprotein cholesterol levels were significantly different between the two measurements (all p<0.05). Cholesterol levels were significantly associated with IMT but not with PWV. Age and systolic blood pressure had a significant impact on both measurements, but the impact on PWV was significantly greater than that on IMT. Indeed, patients with low IMT but with advanced age and high systolic pressure had high PWV, whereas patients with low PWV but with impaired cholesterol levels had high IMT. The extended linear mixed model statistically confirmed that the impact of cardiovascular risk factors on elevated PWV and IMT were not identical in Japanese patients with type 2 diabetes mellitus.
    Journal of atherosclerosis and thrombosis 04/2015; 22(9). DOI:10.5551/jat.29090 · 2.73 Impact Factor
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    ABSTRACT: We longitudinally evaluated the association between monocyte chemoattractant protein-1 (MCP-1) A-2518G polymorphism and new onset of diabetic retinopathy in 758 type 2 diabetic patients. The new onset of retinopathy increased with the increase of the number of G alleles, even after adjustment for age, HbA1c levels, and duration of diabetes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Diabetes Research and Clinical Practice 04/2015; 108(3). DOI:10.1016/j.diabres.2015.04.006 · 2.54 Impact Factor
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    ABSTRACT: To date, promising strategies for treating glucocorticoid (GC)-induced diabetes with antidiabetic drugs have not been established. We herein report the case of a woman with GC-induced diabetes in which we compared the efficacy of two kinds of orally administered antidiabetic drugs sitagliptin and metformin by continuous glucose monitoring (CGM) and meal-challenge test (MCT). As a result, CGM showed that daily fluctuation of blood glucose levels was reduced during administration of metformin but not during administration of sitagliptin. On the other hand, MCT showed that administration of metformin reduced plasma glucose levels accompanied by the decrease of plasma insulin levels and the increase of plasma glucagon levels, whereas administration of sitagliptin had little effects on these parameters. This case is the first report to compare the efficacy between sitagliptin and metformin in glucose homeostasis by CGM and MCT in a patient with GC-induced diabetes.
    Diabetology International 03/2015; DOI:10.1007/s13340-015-0209-z
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    Hideaki Kaneto · Taka-aki Matsuoka ·
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    ABSTRACT: A variety of pancreatic transcription factors including PDX-1 and MafA play crucial roles in the pancreas and function for the maintenance of mature β-cell function. However, when β-cells are chronically exposed to hyperglycemia, expression and/or activities of such transcription factors are reduced, which leads to deterioration of -cell function. These phenomena are well known as β-cell glucose toxicity in practical medicine as well as in the islet biology research area. Here we describe the possible mechanism for β-cell glucose toxicity found in type 2 diabetes. It is likely that reduced expression levels of PDX-1 and MafA lead to suppression of insulin biosynthesis and secretion. In addition, expression levels of incretin receptors (GLP-1 and GIP receptors) in β-cells are decreased, which likely contributes to the impaired incretin effects found in diabetes. Taken together, down-regulation of insulin gene transcription factors and incretin receptors explains, at least in part, the molecular mechanism for β-cell glucose toxicity.
    International Journal of Molecular Sciences 03/2015; 16(3):6281-6297. DOI:10.3390/ijms16036281 · 2.86 Impact Factor
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    ABSTRACT: The murine Mafa transcription factor is a key regulator of postnatal islet β-cell activity, affecting insulin transcription, insulin secretion, and β-cell mass. Human MAFA expression is also markedly decreased in islet β-cells of Type 2 diabetes mellitus (T2DM) patients. Moreover, levels are profoundly reduced in db/db islet β-cells, a mouse model of T2DM. To examine the significance of this key islet β-cell-enriched protein to glycemic control under diabetic conditions, we generated transgenic mice that conditionally and specifically produced Mafa in db/db islet β-cells. Sustained expression of Mafa resulted in significantly lower plasma glucose levels, higher plasma insulin and augmented islet β-cell mass. In addition, there was increased expression of insulin, Slc2a2, and newly identified Mafa regulated genes involved in reducing β-cell stress, like Gsta1 and Gckr. Importantly, the levels of human GSTA1 were also compromised in T2DM islets. Collectively, these results illustrate how consequential the reduction in Mafa activity is to islet β-cell function under pathophysiological conditions. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    Journal of Biological Chemistry 02/2015; 290(12). DOI:10.1074/jbc.M114.595579 · 4.57 Impact Factor
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    ABSTRACT: The current study investigated the association of post-load insulin levels with glucose tolerance in a Japanese population. A total of 1450 Japanese employees who underwent a 75-g oral glucose tolerance test (OGTT) were included. Glucose tolerance was assessed by 120-min glucose levels during a 75-g OGTT. A penalized cubic regression spline model analysis revealed that the 60- and 120-min insulin levels, but not 0- or 30-min insulin levels, had an inverse U-shaped relationship to the 120-min glucose level. Furthermore, peak insulin level followed an inverse U shape in relation to the 120-min glucose level, whereas the peak of insulin appeared at a later point in time as the 120-min glucose level increased. These associations were similarly observed in both obese and non-obese subgroups, although obesity was associated with higher insulin levels. Peak insulin levels also demonstrated an inverse U shape in association with 0-min glucose levels and indices of β cell function, assessed by the disposition index and the β-cell function index. In conclusion, peak insulin levels followed an inverse U shape in relation to glucose intolerance in a Japanese population, whereas the impairment of glucose tolerance was associated with a delay in the time to reach peak insulin levels.
    Endocrine Journal 10/2014; 62(2). DOI:10.1507/endocrj.EJ14-0240 · 2.00 Impact Factor
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    ABSTRACT: It remains to be seen whether pancreatic β cell dysfunction in type 2 diabetic patients can be ameliorated just by correcting hyperglycemia. The current pilot study investigated β cell function after a four-week treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin in Japanese patients with type 2 diabetes mellitus. Ten participants (age, 51 ± 13 years; hemoglobin A1c levels, 9.4 ± 1.0%) took 50 mg of ipragliflozin L-proline for four weeks and thereafter discontinued the agent for one week. A 75-g oral glucose tolerance test (OGTT) was performed at 0 (baseline), 4 (end of medication), and 5 weeks (end of washout). The β cell function was evaluated using the disposition index, which was calculated as the product of the ΔI0-120/ΔG0-120 and the Matsuda index, where ΔI0-120/ΔG0-120 represents the ratio of the incremental concentrations of insulin to those of glucose during the 0- to 120-min time period of the OGTT. The fasting glucose level was 182 ± 34 mg/dl at 0 week, 137 ± 20 mg/dl at 4 weeks (p < 0.001), and 154 ± 31 mg/dl at 5 weeks (p = 0.001). Compared to baseline, the disposition index was significantly elevated not only at 4 weeks (p < 0.001) but also at 5 weeks (p = 0.008). In conclusion, the current pilot study showed that the β cell function assessed by the OGTT-derived disposition index was significantly improved after a four-week treatment with ipragliflozin in Japanese patients with type 2 diabetes mellitus.
    Endocrine Journal 10/2014; 62(1). DOI:10.1507/endocrj.EJ14-0335 · 2.00 Impact Factor

  • Acta Diabetologica 10/2014; 52(3). DOI:10.1007/s00592-014-0657-0 · 2.40 Impact Factor
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    ABSTRACT: Background Brachial-ankle pulse wave velocity (baPWV) is a method to estimate arterial stiffness, which reflects the stiffness of both the aorta and peripheral artery; it would be applicable to general practice, since its measurementis automated. The aim of this study was to evaluate whether baPWV can be predictors of future cardiovascular events (CVE) in diabetic patients.Methods We prospectively evaluated the association between baPWV or carotid intima-media thickness (carotid IMT) at baseline and new onset of CVE in 1040 type 2 diabetic patients without CVE. The predictability of baPWV and/or carotid IMT for identifying patients at high risk for CVE was evaluated by time-dependent receiver-operating-characteristic (ROC) curve analysis.ResultsDuring a median follow-up of 7.5 years, 113 had new CVD events. The cumulative incidence rates of CVE were significantly higher in patients with high baPWV values (¿1550 cm/s) as compared to those with low baPWV values (<1550 cm/s) (p¿<¿0.001, log-rank test). Similarly, the cumulative incidence rate of CVE was significantly higher in patients with higher maximum carotid IMT (maxIMT) values (¿1.0 mm) as compared to those with lower maxIMT values (<1.0 mm) (p¿<¿0.001, log-rank test). Subjects with both ¿high PWV¿ and ¿high IMT¿ had a significantly higher risk of developing CVE as compared to those with either ¿high PWV¿ or ¿high IMT,¿ as well as those with neither. A multivariate Cox proportional hazards regression model revealed that both baPWV (HR¿=¿1.30, [95%CI: 1.07-1.57]; p¿=¿0.009) and maxIMT (HR¿=¿1.20, [95%CI: 1.01-1.41]; p¿=¿0.033) were independent predictors for CVE, even after adjustment for the conventional risk factors. Time-dependent ROC curve analyses revealed that the addition of maxIMT to the Framingham risk score resulted in significant increase in AUC (from 0.60 [95%CI: 0.54-0.67] to 0.63 [95%CI: 0.60-0.82]; p¿=¿0.01). Notably, the addition of baPWV to the Framingham risk score and maxIMT resulted in further and significant (p¿=¿0.02) increase in AUC (0.72 [95%CI: 0.67-0.78]).Conclusions Evaluation of baPWV, in addition to carotid IMT and conventional risk factors, improved the ability to identify the diabetic individuals with high risk for CVE.
    Cardiovascular Diabetology 09/2014; 13(1):128. DOI:10.1186/s12933-014-0128-5 · 4.02 Impact Factor
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    ABSTRACT: The aim of this study was to examine the possible association of vitamin D deficiency with diabetic retinopathy in 75 young Japanese type 1 diabetic patients. A multivariate regression analysis, duration of diabetes and vitamin D deficiency were independent determinants of diabetic retinopathy.
    Diabetes Research and Clinical Practice 08/2014; 106(2). DOI:10.1016/j.diabres.2014.08.005 · 2.54 Impact Factor
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    ABSTRACT: Some type 2 diabetic patients can maintain optimal glycemic control by oral hypoglycemic agents (OHA) after their uncontrolled hyperglycemia is corrected by a temporary introduction of insulin therapy. The objective of this study was to investigate the clinical predictors for the efficacy of OHA after intensive insulin therapy was temporarily introduced. We analyzed a retrospective database of 108 Japanese type 2 diabetic patients who underwent a 75-g oral glucose tolerance test (OGTT) after the temporary introduction of intensive insulin therapy, and tried the switch to OHA. The multivariate logistic regression analysis revealed that shorter diabetic duration, higher body mass index, and lower 2-h post meal glucose levels were independently associated with the efficacy of OHA (all p < 0.001). The C statistic of the multivariate model was calculated to be 0.86. The addition of 120-min insulinogenic index, calculated from 0-, 30-, 60-, and 120-min data during an OGTT, to the model significantly increased the C statistic to 0.91 (p = 0.025). Interestingly, omitting 30- and 60-min data from the calculation of the index did not reduce the predictive performance. Furthermore, the ratio of 120-min insulin levels to 120-min glucose levels also provided a comparable predictive performance. In conclusion, 0- and 120-min data during an OGTT, or even 120-min data alone, in combination with diabetic duration, body mass index, and 2-h post meal glucose levels were useful in predicting the efficacy of OHA after intensive insulin therapy in Japanese type 2 diabetic patients.
    Endocrine Journal 07/2014; 61(9). DOI:10.1507/endocrj.EJ14-0011 · 2.00 Impact Factor
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    ABSTRACT: Type 1 diabetes, one of two major forms of diabetes, results from the complete destruction of pancreatic beta cells. Viral infection has been suggested to be a trigger of beta cell destruction, the pathogenesis of type 1 diabetes. The aim of this study was to clarify the role of the protein encoded by intherferon stimulated gene (ISG) 15, an antiviral effector, in the development of this clinical entity. We used the mouse beta cell line MIN6 to investigate the role of ISG15 and paid special attention to apoptosis. Although not detected in native MIN6 cells, free ISG15 and ISG15 conjugated proteins were both present in dose-dependently increased amounts following stimulation with interferon alpha. As assessed both by caspase 3/7 activity and an annexin V assay, the percentage of apoptotic MIN6 cells (after exposure to the inflammatory cytokines of interleukin-1beta plus interferon gamma or tumor necrosis factor alpha) was decreased by pretreatment with adenovirus-expressing ISG15 and increased by expressing a short hairpin RNA directed against ISG15. In conclusion, ISG15 has an anti-apoptotic effect on MIN6 cells. Thus, promoting ISG15 expression in the pancreatic beta cells could be a potential therapeutic approach for patients with type 1 diabetes.
    Endocrine Journal 07/2014; 61(9). DOI:10.1507/endocrj.EJ14-0219 · 2.00 Impact Factor
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    ABSTRACT: Objective Some diabetic patients have a low toe-brachial index (TBI) despite their normal ankle-brachial index (ABI). We statistically investigated whether the impact of risk factors on TBI would be different compared to ABI. Research design and methods We used a database of 1738 limbs of consecutive 869 Japanese diabetic patients whose ABI and TBI were simultaneously evaluated. We developed a common regression model to ABI and TBI by extending the linear mixed model, and statistically detected the difference in the impact of risk factors between the two indices. Results Sex, smoking, proteinuria, hypertension, and history of stroke and coronary artery disease were common independent risk factors for the decrease of ABI and TBI; their impacts on ABI and TBI were not significantly different. On the other hand, the impact of age, diabetic duration, and body mass index was significantly different between the two indices (all p < 0.05). Age and body mass index were significantly associated with TBI but not with ABI. Diabetic duration had a significant impact both on TBI and ABI, but the impact on TBI was significantly greater than that on ABI (β = −0.144 vs. −0.087; p < 0.05). In the population with normal ABI, patients with these risk factors had a higher prevalence of decreased TBI. Conclusions The risk factors for the decrease of ABI and TBI were not identical in Japanese diabetic patients. Age, diabetic duration and body mass index were associated with reduced TBI in patients with normal ABI.
    Atherosclerosis 07/2014; 235(1):76–80. DOI:10.1016/j.atherosclerosis.2014.04.014 · 3.99 Impact Factor
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    ABSTRACT: Background: Glucose fluctuation often remains to be corrected under basal-supported oral therapy. We investigated the efficacy of adding once-daily rapid-acting insulin in Japanese diabetes patients treated with basal-supported oral therapy. Subjects and methods: In this 8-week, parallel-group, randomized, open-label trial, 62 Japanese adults with type 2 diabetes treated with insulin glargine and 50 mg of sitagliptin were randomized into the following two arms: the single-bolus group, in which once-daily insulin glulisine was initiated at a main meal at a fifth (i.e., 20%) the dose of insulin glargine, and the control group, in which the dose of sitagliptin was maximized to 100 mg. The primary end point was the change of glycemic fluctuation assessed with the M-value. Results: Baseline hemoglobin A1c levels, mean blood glucose profiles, and M-value were 7.2 ± 0.6%, 9.3 ± 1.7 mmol/L, and 21 ± 13 units, respectively. At the end of the study, the single-bolus group had a greater reduction of M-value than the control group (P=0.02); the difference was 6.5 units (95% confidence interval, 1.1-11.9 units). The single-bolus group also had a greater reduction of mean blood glucose levels (P=0.01). There were no significant differences in the incidence of hypoglycemia or the weight change between the two groups (P>0.05). Conclusions: Adding once-daily insulin glulisine was more effective in controlling the glycemic fluctuation in Japanese type 2 diabetes patients treated with insulin glargine together with sitagliptin.
    Diabetes Technology &amp Therapeutics 06/2014; 16(10). DOI:10.1089/dia.2014.0075 · 2.11 Impact Factor
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    ABSTRACT: Objective: Oxidative stress, which is provoked in patients with diabetes, plays critical roles in the pathogenesis of coronary heart disease (CHD). We simultaneously determined 5 relatively common genetic variants related to oxidative stress and evaluated the combined effect on CHD. Methods: We enrolled 1977 Japanese type 2 diabetic subjects without history of CVD (males 66.1%, 59.5 ± 10.0 years old), determined their genotypes regarding glutamate-cysteine ligase modifier subunit (GCLM) C-588T, manganese superoxide dismutase (SOD2) Val16Ala, endothelial nitric oxide synthase (NOS3) G894T, NAD(P)H oxidase p22phox (CYBA) C242T, and myeloperoxidase (MPO) G-463A polymorphisms, and prospectively evaluated the association between these polymorphisms and CHD events. Results: The median follow-up period was 7.5 years and there were 85 new CHD events. The single association analysis revealed that there were no statistically significant associations between each polymorphism and the prevalence of CHD. Interestingly, the risk of CHD event was higher with the increase of the total number of 10 concomitant unfavorable "pro-oxidant alleles" in each subject (p for trend = 0.018, log-rank test). Especially, the carriers of ≥8 pro-oxidant alleles had a significantly increased risk as compared to the carriers of <8 pro-oxidant alleles, whether the other clinical variables were adjusted (HR 2.92 with 95%CI 1.50-5.67, p = 0.002) or not (HR 2.89 with 95%CI 1.49-5.59, p = 0.002).. Conclusions: Accumulation of gene polymorphisms related to oxidative stress is likely associated with the development of CHD in patients with type 2 diabetes, suggesting that the combined information about these variants is useful to assess the risk of CHD.
    Atherosclerosis 06/2014; 235(2):408-414. DOI:10.1016/j.atherosclerosis.2014.05.936 · 3.99 Impact Factor
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    ABSTRACT: While numerous studies have uncovered the molecular mechanisms regulating pancreas development, it remains to be clarified how β cells arise from progenitors, and how recently specified β cells are different from pre-existing β cells. To address these questions, we developed a mouse model in which the insulin 1 promoter drives DsRed-E5 "Timer" fluorescence that shifts its spectrum over time. In the transgenic embryos, green-fluorescent β-cells were readily detected by FACS and could be distinguished from mature β cells only until postnatal day 0, suggesting that β cell neogenesis occurs exclusively during embryogenesis. Transcriptome analysis with green-fluorescent cells sorted by FACS demonstrated that newly differentiated β cells highly expressed progenitor markers, such as Sox9, Neurog3, and Pax4, showing the progenitor-like features of newborn β cells. Flow cytometric analysis of cell cycle dynamics showed that green-fluorescent cells were mostly quiescent, and differentiated β cells were mitotically active. Thus, the precise temporal resolution of this model enables us to dissect the unique features of newly specified insulin-producing cells, which could enhance our understanding of β cell neogenesis for future cell therapy.
    Diabetes 05/2014; 63(10). DOI:10.2337/db13-1312 · 8.10 Impact Factor

Publication Stats

4k Citations
418.72 Total Impact Points


  • 2014
    • The University of Tokushima
      • Diabetes Therapeutics and Research Center
      Tokusima, Tokushima, Japan
  • 2006-2014
    • Osaka University
      • • Division of Metabolic Medicine
      • • Department of Internal Medicine
      • • Graduate School of Medicine
      Suika, Ōsaka, Japan
  • 1999-2014
    • Osaka City University
      • Graduate School of Medicine
      Ōsaka, Ōsaka, Japan
  • 2003-2005
    • Vanderbilt University
      • Department of Molecular Physiology and Biophysics
      Nashville, Michigan, United States