Taka-Aki Matsuoka

The University of Tokushima, Tokusima, Tokushima, Japan

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Publications (112)449.6 Total impact

  • [Show abstract] [Hide abstract]
    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; · 4.60 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; · 2.02 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; · 2.02 Impact Factor
  • Acta diabetologica. 10/2014;
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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. · 3.71 Impact Factor
    This article is viewable in ResearchGate's enriched format
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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; · 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; · 2.02 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; · 2.02 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. · 3.71 Impact Factor
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    ABSTRACT: 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; · 2.29 Impact Factor
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    ABSTRACT: 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.
    Atherosclerosis 06/2014; 235(2):408-414. · 3.71 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). · 7.90 Impact Factor
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    ABSTRACT: We investigated whether 10 mg per day of azilsartan, one-half of the normal dosage, would be non-inferior to 8 mg per day of candesartan cilexetil for controlling blood pressure in Japanese patients with hypertension. In this open-label, randomized, crossover trial, 309 hypertensive Japanese adults treated with 8-mg candesartan cilexetil were randomized into two arms and received either 10-mg azilsartan or 8-mg candesartan cilexetil in a crossover manner. The primary efficacy outcome was systolic blood pressure, and the margin of non-inferiority was set to be 2.5 mm Hg. The participants were 67±11 years old, and 180 (58%) were male. The baseline systolic and diastolic blood pressure levels were 127.1±13.2 and 69.7±11.2 mm Hg, respectively. During the study period, the difference in systolic blood pressure between the treatments with 10-mg azilsartan and 8-mg candesartan cilexetil was -1.7 mm Hg, with the two-sided 95% confidence interval (CI) ranged from -3.2 to -0.2 mm Hg. The upper boundary of the 95% CI was below the margin of 2.5 mm Hg, confirming the non-inferiority of 10-mg azilsartan to 8-mg candesartan cilexetil. The difference also reached significance (P=0.037). The corresponding difference in diastolic blood pressure was -1.4 (95% CI: -2.4 to -0.4) mm Hg (P=0.006). Treatment with 10-mg azilsartan was similar to 8-mg candesartan cilexetil in its association with rare adverse events. In conclusion, 10-mg azilsartan was non-inferior to 8-mg candesartan cilexetil for controlling systolic blood pressure in Japanese hypertensive patients already being treated with 8-mg candesartan cilexetil.Hypertension Research advance online publication, 17 April 2014; doi:10.1038/hr.2014.86.
    Hypertension Research 04/2014; · 2.94 Impact Factor
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    ABSTRACT: We investigated the efficacy of once- and thrice-daily voglibose, an alpha-glucosidase inhibitor, as an add-on therapy to alogliptin, a dipeptidyl peptidase-4 inhibitor, on glycemic control in Japanese type 2 diabetic patients. In this 12-week, parallel-group, randomized, open-label, three-arm trial, 151 participants treated with alogliptin were randomly allocated to the following three arms; one was the group to initiate once-daily voglibose, another was to initiate thrice daily voglibose, and the other was the control group. The primary endpoint was the change of hemoglobin A1c levels at the end of the study, which was revealed to be significantly different among groups (p < 0.001). The once- and thrice-daily voglibose groups had a significantly greater reduction than the control group; the difference was -0.27% and -0.33% in the once- and thrice-daily voglibose group, respectively (both p < 0.001). No significant difference was observed between the two voglibose groups (p = 0.615). On the other hand, the increase of 1,5-anhydroglucitol levels were 3.3 and 5.5 μg/ml greater in the once- and thrice-daily voglibose groups than the control group (both p < 0.001). The thrice-daily voglibose group had a greater increase of 1,5- anhydroglucitol levels compared to the once-daily voglibose group (p = 0.005). In conclusion, once- and thrice-daily voglibose as an add-on to alogliptin significantly improved glycemic control in Japanese type 2 diabetic patients.
    Endocrine Journal 02/2014; · 2.02 Impact Factor
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    ABSTRACT: The current study compared the vibratory sensations at different sites, using a retrospective database of 547 Japanese diabetic patients. The vibratory sensation was assessed with a 128-Hz tuning fork at the medial malleolus, the great toe and the fifth toe. The vibratory sensations at different sites were significantly associated with one another (all P < 0.01). The vibratory sensation at one site corresponding to 10 s at another site was calculated to be 9-11 s. Although the vibratory sensations at the three sites had different associations with the pressure sensation and the ankle reflex, they showed similar C-statistics for the impaired pressure sensation and the disappeared ankle reflex. In conclusion, the vibratory sensations at different sites were strongly associated with one another. They would be clinically acceptable alternatives to one another in the assessment of diabetic peripheral neuropathy.
    Journal of Diabetes Investigstion 02/2014; 5(1):90-3. · 1.50 Impact Factor
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    ABSTRACT: While the exogenous expression of a combination of transcription factors have been shown to induce the conversion of non-β cells into insulin-producing cells, the reprogramming efficiency remains still low. In order to develop an in vitro screening system for an optimized reprogramming protocol, we generated the reporter cell line mPac-MIP-RFP in which the reprogramming efficiency can be quantified with red fluorescent protein expressed under the control of the insulin promoter. Analysis with mPac-MIP-RFP cells sequentially infected with adenoviruses expressing Pdx1, Neurog3, and Mafa revealed that expression of Pdx1 prior to Neurog3 or Mafa augments the reprogramming efficiency. Next, infection with a polycistronic adenoviral vector expressing Pdx1, Neurog3 and Mafa significantly increased the expression level of insulin compared with the simultaneous infection of three adenoviruses carrying each transcription factor, although excessive expression of Mafa together with the polycistronic vector dramatically inhibited the reprogramming into insulin-producing cells. Thus, in vitro screening with the mPac-MIP-RFP reporter cell line demonstrated that the timing and dosage of gene delivery with defined transcription factors influence the reprogramming efficiency. Further investigation should optimize the reprogramming conditions for the future cell therapy of diabetes.
    Biochemical and Biophysical Research Communications 01/2014; · 2.28 Impact Factor
  • Hideaki Kaneto, Taka-Aki Matsuoka
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    ABSTRACT: Type 2 diabetes is one of the most prevalent and serious metabolic diseases. Under diabetic conditions, chronic hyperglycemia and subsequent induction of oxidative stress deteriorate pancreatic β-cell function, which leads to the aggravation of type 2 diabetes. Although such phenomena are well known as glucose toxicity, its molecular mechanism remains unclear. In this review article, we describe the possible molecular mechanism for β-cell dysfunction found in type 2 diabetes, focusing on (1) oxidative stress, (2) pancreatic transcription factors (PDX-1 and MafA) and (3) incretin receptors (GLP-1 and GIP receptors). Under such conditions, nuclear expression levels of PDX-1 and MafA are decreased, which leads to suppression of insulin biosynthesis and secretion. In addition, expression levels of GLP-1 and GIP receptors are decreased, which likely contributes to the impaired incretin effects found in diabetes. Taken together, it is likely that down-regulation of pancreatic transcription factors (PDX-1 and MafA) and down-regulation of incretin receptors (GLP-1 and GIP receptors) explain, at least in part, the molecular mechanism for β-cell dysfunction found in type 2 diabetes.
    World journal of diabetes. 12/2013; 4(6):263-269.
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    ABSTRACT: Although chronic pain due to diabetic neuropathy, defined as painful diabetic neuropathy (PDN), is a debilitating and distressing complication of diabetes, epidemiological data on PDN has been scarce, especially in Asia. We evaluated the prevalence of Japanese PDN and its impact on their quality of life (QOL) and metnal state. In addition, we examined to which extent physicians are aware of patients' PDN. A total of 298 patients with diabetes were found to be eligible for the study. We revealed that substantial percentage (22.1%) of Japanese diabetic patients had PDN and that PDN had negative effect on patients' QOL and mental state. However, physicians were aware of PDN in only 36.4% of patients with the condition. To the best of our knowledge, this is the first report showing the extent of physicians' awareness of patients' PDN. In conclusion, physicians treating diabetes need to be more aware of patients' PDN in everyday clinical practice to prevent the progression of PDN and improve the patients' QOL and mental state.
    Pain research and treatment. 11/2013; 2013:318352.
    This article is viewable in ResearchGate's enriched format
  • Journal of Biological Chemistry 10/2013; 288(43):31298. · 4.60 Impact Factor
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    ABSTRACT: 5-Hydroxytryptamine type 2 antagonists are used to treat symptomatic peripheral arterial disease. However, it remains unknown as to whether the administration of sarpogrelate, a 5-hydroxytryptamine type 2 antagonist, improves the prognosis after endovascular therapy for critical limb ischemia (CLI). We performed a retrospective analysis using a database of 386 Japanese patients undergoing endovascular therapy for CLI. Sixty-seven patients were treated with sarpogrelate, and we compared their prognosis with that of an equal number of background-matched controls extracted from the population. The primary end point was the first event of either major amputation or death from any cause, and amputation-free survival was evaluated. The follow-up period was 21 ± 18 months (mean ± standard deviation), and 58 end points were observed. Patients treated with sarpogrelate had a significantly higher amputation-free survival rate than their matched controls (P = 0.036). The hazard ratio for the end point and its 95 % confidence interval was 0.57 (0.34-0.97). These results suggest that sarpogrelate treatment is associated with a favorable prognostic outcome in CLI patients undergoing endovascular therapy. Future prospective studies are required to investigate whether sarpogrelate treatment would improve the prognosis of CLI patients.
    Heart and Vessels 03/2013; · 2.13 Impact Factor

Publication Stats

4k Citations
449.60 Total Impact Points


  • 2012–2014
    • The University of Tokushima
      • Diabetes Therapeutics and Research Center
      Tokusima, Tokushima, Japan
  • 1999–2014
    • Osaka City University
      • Graduate School of Medicine
      Ōsaka, Ōsaka, Japan
  • 1997–2012
    • Osaka University
      • • Division of Metabolic Medicine
      • • Department of Integrated Medicine
      Suika, Ōsaka, Japan
  • 2003–2005
    • Vanderbilt University
      • Department of Molecular Physiology and Biophysics
      Nashville, Michigan, United States