Y Yamasaki

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..We evaluated the prognostic value of gated myocardial perfusion single-photon computed tomography (SPECT) for asymptomatic diabetic patients in a Japanese population...

..An open randomized prospective study was performed to elucidate the effect of an alpha-glucosidase inhibitor, voglibose, on the progression of atherosclerosis in subjects with type 2 diabetes...

..However, the synergistic effects of SNPs have not been evaluated in detail...

..This prospective, 2-year follow-up study was designed to determine the efficacy and safety of antiplatelet therapy in the prevention of atherosclerosis of diabetic subjects...

..Thus, there seems to be a racial difference in vulnerability to toxic nerve agents, such as sarin. The dominance of the Arg192 allele in the Japanese population probably worsened the tragedy of March 1995 in the Tokyo subway...

..To examine carotid intima-media thickness (IMT), predictors of its progression, and its relationship with incident coronary heart disease (CHD) in type 2 diabetic Japanese patients...

..This means that other components constituting the transcription-controlling machinery need to be evaluated in order to understand the molecular basis of impaired insulin biosynthesis such as that observed due to glucose toxicity...

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..0003). In conclusion, accumulation of oxidative stress-associated alleles was associated with carotid atherosclerosis in type 2 diabetic patients...

..CONCLUSIONS/INTERPRETATION: These data indicate that metformin or gliclazide, rather than glibenclamide, have a potent anti-atherogenic effect in type 2 diabetes...

..A basal insulin supplement alone was not effective. The effectiveness of a prandial insulin supplement may have been further improved by a combined basal and meal-related treatment program...

..The aim of this study was to estimate sCD40L levels in type 1 diabetic patients to examine a possible association with carotid atherosclerosis...

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..Interestingly, the location and pattern of aa deletions are identical to those previously described for the aa polymorphism within the human counterpart, E47 (E12) [Kamps et al., Cell 60 (1990) 547-555]...

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..The conditional PDX-1 transgenic mouse system developed in this study appeared to be useful for efficient screening of PDX-1 responsive somatic tissues and cells...

..In conclusion, the regeneration process of beta-cells varied by circumstance. Our mouse model is useful for studying the mechanism of regeneration, since differentiation and proliferation could be analyzed separately in one pancreas...

..05-1.17, P=0.0002). We concluded that diabetic retinopathy is related to diabetic duration and high heart rate in type 2 diabetes mellitus with normoalbuminuria. Heart rate elevation may be a predictor of advanced retinopathy...

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..Taken together, Foxo1 is involved in the nucleocytoplasmic translocation of PDX-1 by oxidative stress and the JNK pathway...

..The aim of this study was to examine a possible association of two eNOS polymorphisms, Glu298Asp (G894T) in exon 7 and (-)786T-C mutation with insulin resistance...

..The variation in the A1/kA1 expression ratios, on the other hand, supports the idea that A1 (E47) and kA1 (E12) each have some unique roles in the functions of these E2A gene-encoded bHLH proteins...

..Also, an increase in intima-media thickness of the carotid artery wall could be able to predict the onset of silent brain infarction...

..05); glucose, 44.6+/-2.4 vs. 35.2+/-2.6 mmol/l (120 min, at 16 weeks; P<0.05). Thus, our present observations demonstrate the potential usefulness of probucol for treatment of type 2 diabetes...

..These observations suggest the involvement of multiple enzymes in the regulation of cADPR concentrations in pancreatic islet cells...

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..This transgenic mouse model would be useful to non-invasively monitor in vivo pdx-1 promoter activity and to screen new molecules which regulate PDX-1 expression...

..Nateglinide ameliorates insulin resistance as well as insulin secretory defects in type 2 diabetic patients...

..Our present observations demonstrate a unique role of STAT3 in maintaining glucose-mediated early-phase insulin secretion and normal islet morphology...

..Thus, the c-Jun N-terminal kinase pathway plays a central role in pathogenesis of type 2 diabetes and could be a potential target for diabetes therapy...

..Taken together, our present observations suggest that heterozygous mutations in the PAX6 gene can induce eye anomaly and glucose intolerance in individuals harboring these mutations...

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..These data indicate that pioglitazone treatment suppresses ER stress in the liver which may explain, at least in part, the pharmacological effects of pioglitazone to reduce insulin resistance...

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..These observations suggest the involvement of PDX-1 in human IAPP gene regulation, which seems to be mediated through at least two A element-like cis-motifs in the gene promoter...

..These results suggest that methylguanidine inhibits insulin binding to its receptor, resulting in decreased insulin binding to erythrocytes...

..It is likely that alteration of such transcription factors explains, at least in part, the molecular mechanism for beta-cell glucose toxicity found in diabetes...

..These results suggest that sEH and EDHF play some important role in the pathogenesis of insulin resistance found in type 2 diabetes...

..These results imply that Rho/Rho-kinase activation is involved in the suppression of insulin expression found in diabetes and that suppression of the Rho/Rho-kinase pathway could be a useful tool to augment insulin gene transcription...

..28, P<0.001). In summary, GA could be a better marker for glycemic control than glycated hemoglobin in diabetic patients, especially for evaluating glycemic excursion, which is considered to be a major cause of diabetic angiopathy...

..CONCLUSIONS: Anti-ORP150 autoantibody levels in Type 1 diabetic patients are higher compared with non-diabetic subjects, suggesting that ER stress is increased in Type 1 diabetes...

..We simultaneously determined 5 relatively common genetic variants related to oxidative stress and evaluated the combined effect on MI...

..535, P=0.005 versus r=-0.461, P=0.010). We would therefore like to propose a novel index, HOMA-AD, as a simple and adequate index for determining insulin resistance even in diabetic patients with overt hyperglycemia...

..The prevalence of diabetic retinopathy was higher as the number of G alleles increased, suggesting that the G allele of this polymorphism is a susceptibility allele for diabetic retinopathy...

..898, 95%CI: 0.811-0.994, p=0.0374). These results suggest that clustering of the cardiovascular risk factors affects the Calibrated-IBS, an acoustic parameter of tissue characteristics of the intima-media complex in the carotid artery...

..The present analysis may provide one approach to evaluate combination of multiple genetic risk factors, which is synergistically associated with carotid atherosclerosis and myocardial infarction...

..Taken together, it is likely that oxidative stress and subsequent activation of the JNK pathway are involved in the pathogenesis of type 1 and type 2 diabetes...

..The combination of PDX-1, BETA2, and MafA also induced the expression of other important regulators of islet beta-cell activity. These results support a critical role of MafA in islet beta-cell function...

..Thus, it is likely that alteration of such transcription factors explains, at least in part, the molecular mechanism for beta-cell glucose toxicity found in diabetes...

..Taken together, the JNK pathway plays a crucial role in progression of insulin resistance as well as beta-cell dysfunction found in diabetes and thus could be a potential therapeutic target for diabetes...

..In addition, our present results suggest that ERAI transgenic mice are very useful for evaluating in vivo ER stress, especially in the liver, during the development of insulin resistance...

..Taken together, it is likely that oxidative stress and subsequent activation of the JNK pathway are involved in the pathogenesis of type 1 and type 2 diabetes...

..It is likely that circulating sRAGE and esRAGE are distinct markers and that circulating esRAGE levels, but not sRAGE levels, are associated with the status of early-stage atherosclerosis...

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..However, there have been few reports about the usefulness of these indices for the assessment of early stage atherosclerosis in Japanese type 2 diabetic subjects...

..We simultaneously determined four relatively common genetic variants related to plaque rupture or subsequent local thrombus formation and evaluated the combined effect on cerebral infarction...

..38+/-3.87 microg/ml) compared to the patients without it (n=57, 7.68+/-2.80 microg/ml) (p=0.0013). Elevated PEDF levels may be related to the progression of diabetic retinopathy...

..Both the size and tissue characteristics of the carotid plaque may identify subjects with a high risk of cardiovascular disease...

..Thus PDX-1/VP16 expression, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. This approach warrants further investigation and may have utility in the treatment of diabetes...

..Thus, the c-Jun N-terminal kinase pathway plays a central role in pathogenesis of type 2 diabetes and could be a potential target for diabetes therapy...

..These results suggest a crucial role of MafA as a novel therapeutic target for diabetes...

..In conclusion, post-prandial hyperglycemia, rather than fasting glycemia or hemoglobin A1c levels, is an important predictor of the incidence of diabetic microangiopathy in Japanese type 2 diabetic patients...

..The aim of the present study is to longitudinally evaluate the association between esRAGE and sRAGE levels and the progression of carotid intima-media thickness (IMT), a surrogate marker of atherosclerosis...

..In the present study, we examined circulating endogenous secretory RAGE (esRAGE) levels in subjects with type 1 diabetes and explored the possible association between esRAGE levels and the severity of diabetic vascular complications...

..Taken together, the oxidative stress-mediated activation of the JNK pathway leads to nucleocytoplasmic translocation of PDX-1 and thus is likely involved in the progression of beta-cell dysfunction found in diabetes...

..33 v 1.03 +/- 0.17, P <.05). We conclude that BDNF mainly improves hepatic insulin resistance in obese insulin-resistant rats, probably by affecting the hepatic GK flux. Copyright 2003, Elsevier Science (USA). All rights reserved...

..This is the first report showing that ER stress plays a crucial role in the insulin resistance found in diabetes and thus could be a potential therapeutic target for diabetes...

..These data indicate that the JNK pathway is critically involved in diabetes and that the cell-permeable JNK-inhibitory peptide may have promise as a new therapeutic agent for diabetes...

..Thus, the JNK pathway plays a central role in pathogenesis of type 2 diabetes and may be a potential target for diabetes therapy...

..Taken together, these findings suggest that suppression of the JNK pathway in liver exerts greatly beneficial effects on insulin resistance status and glucose tolerance in both genetic and dietary models of diabetes...

..Impaired hepatic glucose uptake associated with elevated FFA may contribute to the development of insulin resistance in obesity and type 2 diabetes...

..These data clearly indicate that several genetic risk factors as well as conventional risk factors additively or synergistically contribute to diabetic macroangiopathy...

..These results provide a mechanism of pancreatic metaplasia by which persistent PDX-1 expression cell-autonomously induces acinar-to-ductal transition through Stat3 activation...

..CONCLUSIONS: Our data indicate that hs-CRP levels are elevated in young patients with type 1 diabetes, possibly corresponding with early-stage advanced carotid atherosclerosis...

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..These observations support the idea that multiple defects of the glucose-responsive insulin secreting machinery are involved in the development of diabetes in GK rats...

..The intrinsic PKC activity in SK-N-MC cells should play a major role in the constitutive, high expression of IGF-I and may therefore contribute in part to the maintenance of the tumor phenotype of the cells...

..However, the efficacy and usefulness of 2 different antiplatelet drugs, aspirin and cilostazol, in the progression of carotid intima-media thickening are unknown...

..Since NODAT patients have advanced arterial stiffness probably due to high blood pressure, strict control of blood pressure will be important for preventing the development of cardiovascular disease in NODAT...

..After administration of these insulin, insulin was absorbed as rapid as intra-muscular injection of insulin and thus could effectively control postprandial glycemic excursion in diabetic patients...

..02) but not with GIR. These data demonstrate that an acute insulin load stimulates cardiac SNA, and insulin sensitivity in the regulation of SNA may be associated with BP regulation independently of peripheral insulin sensitivity...

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..Furthermore, ORP150 enhanced the insulin sensitivity of myoblast cells treated with hydrogen peroxide. These data suggest that ORP150 plays an important role in insulin sensitivity and is a potential target for the treatment of diabetes...

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