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Biomedical subjects

Yoshifumi Tamura

Publications and source records attributed to Yoshifumi Tamura.

12 recordsLinked to original sources

Comparison of glycated albumin (GA) and glycated hemoglobin (HbA1c) in type 2 diabetic patients: usefulness of GA for evaluation of short-term changes in glycemic control.

We studied the cross-sectional relationship between GA and HbA1c in 142 type 2 diabetic patients who had an HbA1c level < 7.5% for at least one year without fluctuation by more than 0.5%. We also followed the changes of GA and HbA1c in 18 type 2 diabetic patients for 16 weeks as they progressed from untreated severe hyperglycemia (HbA1c > or = 9.0%) to good glycemic control (HbA1c < or = 6.5%) by intensive insulin treatment. The annual mean levels of GA and HbA1c in the stably controlled patients showed a weak, but significant, correlation (r = 0.23, p<0.001) in the 142 diabetic patients. However, the GA/HbA1c ratio ranged widely from 2.0 to 4.0 showing a normal distribution (2.9 +/- 0.34, M +/- SE), although patients with conditions affecting albumin turnover or RBC lifespan were excluded from the study. The GA/HbA1c ratio was significantly higher when patients were in hyperglycemic than when glycemic control was good (3.5 +/- 0.15 vs. 2.9 +/- 0.07, M +/- SE, p<0.01). GA decreased more rapidly than HbA1c during intensive insulin therapy, but the percent reduction of HbA1c eventually corresponded with that of GA by 16 weeks after the start of treatment. These results demonstrate that, although unknown influences on GA or HbA1c may exist, GA may be a useful marker for monitoring short-term variations of glycemic control during treatment of diabetic patients.

Aged↗

Protein kinase Cdelta plays a non-redundant role in insulin secretion in pancreatic beta cells.

Protein kinase C (PKC) is considered to modulate glucose-stimulated insulin secretion. Pancreatic beta cells express multiple isoforms of PKCs; however, the role of each isoform in glucose-stimulated insulin secretion remains controversial. In this study we investigated the role of PKCdelta, a major isoform expressed in pancreatic beta cells on beta cell function. Here, we showed that PKCdelta null mice manifested glucose intolerance with impaired insulin secretion. Insulin tolerance test showed no decrease in insulin sensitivity in PKCdelta null mice. Studies using islets isolated from these mice demonstrated decreased glucose- and KCl-stimulated insulin secretion. Perifusion studies indicated that mainly the second phase of insulin secretion was decreased. On the other hand, glucose-induced influx of Ca2+ into beta cells was not altered. Immunohistochemistry using total internal reflection fluorescence microscopy and electron microscopic analysis showed an increased number of insulin granules close to the plasma membrane in beta cells of PKCdelta null mice. Although PKC is thought to phosphorylate Munc18-1 and facilitate soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors complex formation, the phosphorylation of Munc18-1 by glucose stimulation was decreased in islets of PKCdelta null mice. We conclude that PKCdelta plays a non-redundant role in glucose-stimulated insulin secretion. The impaired insulin secretion in PKCdelta null mice is associated with reduced phosphorylation of Munc18-1.

Animals↗

Strict glycemic control ameliorates the increase of carotid IMT in patients with type 2 diabetes.

The aim of this study was to investigate the effect of strict glycemic control on the carotid artery intima-media thickness (IMT) in type 2 diabetic patients who initially had good glycemic control (HbA1c between 5.8 and 6.4 %). The subjects were 67 patients showing deterioration of the mean HbA1c over 3 years by more than 0.2% from baseline (D group) and 33 subjects showing improvement of the mean HbA1c by more than 0.2% from baseline (A group). The clinical characteristics and annual change of IMT during the observation period were compared between the two groups in a 3-year retrospective longitudinal study. The baseline characteristics and the mean values of BMI, blood pressure, and serum lipids during the study period did not differ significantly between the two groups. However, the mean HbA1c of A group was significantly lower than that of D group (5.67 +/- 0.10 vs. 6.28 +/- 0.08, mean +/- SE, p<0.001). The adjusted annual increase rate of IMT was significantly less in A group than in D group (-0.035 +/- 0.019 vs. 0.036 +/- 0.015 mm, M +/- SEM, p<0.001). These results indicate that further improvement of glycemic control from a good HbA1c value can prevent an increase of IMT in type 2 diabetic patients.

Adult↗

[Insulin resistance].

Insulin resistance is closely associated with fat accumulation in liver. Thus, it has been suggested that insulin resistance is one of the important factor in development of non-alcoholic steatohepatitis(NASH). For example, insulin resistance in adipocyte results in increased lipolysis and delivery of free fatty acids(FFAs) to the liver, which induce fatty liver. If there is insulin resistance in skeletal muscle, hyperinsulinemia and/or hyperglycemia might increase fat accumulation in liver, through, at least in part, increased sterol-regulatory element binding protein-1c(SREBP-1c) activation. However, hepatic insulin resistance might prevent fat accumulation in liver, because insulin strongly induces lipogenesis. Thus, the tissue specific insulin resistance should be considered in the pathogenesis of NASH.

Adipocytes↗

N-(carboxymethyl)valine residues in hemoglobin (CMV-Hb) reflect accumulation of oxidative stress in diabetic patients.

While carboxymethylated proteins are considered to be advanced glycation end products (AGE), they can also be induced by reactive oxygen species (ROS) independently of the AGE-forming process. To clarify whether N-(carboxymethyl)valine residues in hemoglobin (CMV-Hb) were a useful marker of the accumulation of ROS in diabetes, we evaluated CMV-Hb formation in vitro and in vivo. For the in vitro studying, purified human hemoglobin was incubated with D-glucose or D-glucose and hydrogen peroxide. For the in vivo study, CMV-Hb was extracted from peripheral red blood cells in diabetic patients and compared with that from non-diabetic subjects. Furthermore, the effect of antioxidants was evaluated after 6 months in 15 diabetic patients showing very high CMV-Hb levels. In vitro CMV-Hb formation increased in a glucose concentration and time-dependent manner. Co-incubation with glucose and hydrogen peroxide synergistically increased CMV-Hb formation. The CMV-Hb level was higher in the diabetic group than the non-diabetic group, and CMV-Hb was correlated with the plasma total cholesterol and serum creatinine levels. The CMV-Hb level was decreased by antioxidant therapy, whereas HbA1c did not change. These results demonstrate that CMV-Hb may be a useful marker for accumulation of oxidative stress in diabetic patients.

Diabetes Mellitus, Type 2↗

Effects of diet and exercise on muscle and liver intracellular lipid contents and insulin sensitivity in type 2 diabetic patients.

Insulin resistance is associated with the circulating free fatty acid (FFA) level and intracellular lipid content in muscle and liver. We investigated the effect of 2-wk diet and exercise therapy on total adiposity, circulating FFA, intracellular lipid content in muscle and liver, and peripheral insulin sensitivity. Type 2 diabetic patients were divided into a diet group (n = 7) and a diet plus exercise group (n = 7). We performed a hyperinsulinemic-euglycemic clamp study before and after treatment. Intramyocellular lipid (IMCL) in the tibialis anterior muscle and intrahepatic lipid (IHL) were evaluated by (1)H-magnetic resonance spectroscopy. Fasting FFA were not altered, and total body fat showed a slight, but significant, decrease in both groups after treatment. IMCL was decreased by 19%, and the glucose infusion rate was increased by 57% in the diet plus exercise group, whereas neither IMCL nor glucose infusion rate was significantly altered in the diet group. However, IHL showed a significant decrease in both groups. In summary, we found that 2 wk of diet and exercise decreased IMCL and increased muscle insulin-mediated glucose uptake, whereas diet with or without exercise decreased IHL. These effects were evident despite a small decrease in body fat and were observed independently of fasting FFA levels.

Blood Glucose↗

Inhibitory effect of mizoribine on matrix metalloproteinase-1 production in synovial fibroblasts and THP-1 macrophages.

To investigate the mechanism of antirheumatic action of mizoribine (MZR), we examined the expression of matrix metalloproteinase-1 (MMP-1) and MMP-3 utilizing THP-1 derived macrophage-like cells (THP-1 macrophages) and human synovial fibroblasts (SFs). The cells were respectively stimulated with lipopolysaccharide (LPS) and interleukin-1beta in the presence or absence of MZR in vitro. The concentrations of MMP-1 and MMP-3 in the supernatant were measured by enzyme-linked immunosorbent assay. The secretion of MMP-1 from SFs, as well as THP-1 macrophages, was inhibited by MZR in a dose-dependent manner. Furthermore, a quantitative real-time polymerase chain reaction revealed that MZR decreased the expression of MMP-1 messenger RNA. These findings may be an explanation for the clinical effect of MZR in patients with rheumatoid arthritis.

Journal Article↗

Responsiveness of insulin-induced cardiac sympathetic nerve activation associates with blood pressure regulation in diabetics.

To quantitatively evaluate the effect of insulin on cardiac sympathetic nerve activity (SNA) and analyze clinical factors associated with insulin sensitivity for the regulation of SNA in diabetics, 29 Japanese type 2 diabetics without neuropathy were recruited. A 2-h control study and a 2-h hyperinsulinemic euglycemic glucose clamp study were performed. From the power spectral analysis of R-R intervals on ECG during both studies, two major components, the low-frequency (LF) and the high-frequency component (HF), were obtained. Then %LF was calculated as LF/(LF +HF), and the ratio of the average %LF during the last 30 min of the clamp or the control to the average %LF for the entire time for clamp or control (R-%LF) was used as a marker of changes in SNA. R-%LF was significantly higher during the clamp than in the control (1.07 +/- 0.04 vs. 1.03 +/- 0.03, P < 0.05). High responders (individual R-%LF during clamp > or = mean + 2SD in control) showed a higher basal mean blood pressure (BP) before the clamp (89 +/- 3 vs. 82 +/- 2, P < 0.03) but not a higher glucose infusion rate (GIR) compared with low responders (<mean + 2SD). Furthermore, R-%LF showed a positive correlation with basal mean BP (P < 0.02) 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.

Adult↗

Development of internal transcribed spacer regions amplification restriction fragment length polymorphism method and its application in monitoring the population of Zygosaccharomyces rouxii M2 in miso fermentation.

Recently, the use of the dry yeast of Zygosaccharomyces rouxii M2 for miso (soybean paste) fermentation has been established. A molecular monitoring method was developed and validated in this study to analyze the population of Z. rouxii M2 during the fermentation. The method was based on the restriction patterns of internal transcribed spacer (ITS) regions of the rDNA using HaeIII and HhaI. Among the homologous ITS regions of Z. rouxii strains, Z. rouxii M2 produced diagnostic bands by which it can be differentiated from the other strains used. The specific restriction bands were due to the difference in nucleotide sequence of two different copies of ITS of Z. rouxii M2. Both ITS copies showed 94% sequence similarity but a 13-bp nucleotide substitution and a 19-bp deletion were found in the ITS1 region. Phylogenetic trees were constructed based on ITS and 18S rDNA sequences and it was found that the ITS sequences provide better resolution for the classification of Z. rouxii M2. Since Z. rouxii M2 is a promising strain for use in miso fermentation as a dry starter, the method developed is significant in terms of industrial application in monitoring the growth of Z. rouxii M2 in miso fermentation.

Journal Article↗

Changes in the concentrations of bioactive compounds in plantain leaves.

The plantain is used in herbal medicines and for pasturage. Two cultivars of plantain (Plantago lanceolata L.), Grasslands Lancelot and Ceres Tonic, were sown in spring. Changes in catalpol, aucubin, and acteoside concentrations in the leaves during the growing season and by drying after harvesting were quantitatively determined by high-performance liquid chromatography. The concentration of catalpol was relatively low, fluctuating between 1 and 2% of dry matter during the growing season, and there was no clear-cut seasonal change. From spring to midfall, the aucubin concentration increased from 2.1 to 4.8% in Grasslands Lancelot and from 1.0 to 2.7% in Ceres Tonic. These increases were gradual over the season, except for during midsummer, when aucubin concentrations were relatively constant. The acteoside concentration increased from 3.4 to 7.1% in Grasslands Lancelot and from 1.5 to 4.1% in Ceres Tonic over the course of the growing season, although in the summer it declined steadily to lows of 2.5% in Grasslands Lancelot and 1.9% in Ceres Tonic. Our data suggested that midfall was the appropriate time for harvesting plantain for medicinal use. The concentrations of the bioactive compounds steadily decreased in the initial stages of drying both under natural climatic conditions and at 60 degrees C. The development of processing methods to minimize the loss of bioactive compounds is imperative.

Chromatography, High Pressure Liquid↗

The composition of dietary fat directly influences glucose-stimulated insulin secretion in rats.

Acute elevations of plasma free fatty acid (FFA) levels augment glucose-stimulated insulin secretion (GSIS). Prolonged elevations of FFA levels reportedly impair GSIS, but no one has previously compared GSIS after prolonged exposure to saturated or unsaturated fat. Rats received a low-fat diet (Low-Fat) or one enriched with either saturated (Lard) or unsaturated fat (Soy) for 4 weeks. Insulin responses during hyperglycemic clamps were augmented by saturated but not unsaturated fat (580 +/- 25, 325 +/- 30, and 380 +/- 50 pmol x l(-1) x min(-1) in Lard, Soy, and Low-Fat groups, respectively). Despite hyperinsulinemia, the amount of glucose infused was lower in the Lard compared with the Low-Fat group. Separate studies measured GSIS from the perfused pancreas. Without fatty acids in the perfusate, insulin output in the Lard group (135 +/- 22 ng/30 min) matched that of Low-Fat rats (115 +/- 13 ng/30 min), but exceeded that of Soy rats (80 +/- 7 ng/30 min). When FFAs in the perfusate mimicked the quantity and composition of plasma FFAs in intact animals, in vivo insulin secretory patterns were restored. Because the GSIS of rats consuming Lard diets consistently exceeded that of the Soy group, we also assessed responses after 48-h infusions of lard or soy oil. Again, lard oil exhibited greater insulinotropic potency. These data indicate that prolonged exposure to saturated fat enhances GSIS (but this does not entirely compensate for insulin resistance), whereas unsaturated fat, given in the diet or by infusion, impairs GSIS. Inferences regarding the impact of fatty acids on GSIS that are based on models using unsaturated fat may not reflect the effects of saturated fat.

Animals↗