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Biomedical subjects

N Tajima

Publications and source records attributed to N Tajima.

At least 19 recordsLinked to original sources
PubMed2006

Ghrelin prevents development of diabetes at adult age in streptozotocin-treated newborn rats.

AIMS/HYPOTHESIS: Ghrelin, a stomach-derived hormone, functions in multiple biological processes, including glucose metabolism and cellular differentiation and proliferation. In this study, we examined whether early treatment with ghrelin can regenerate beta cells of the pancreas in an animal model of diabetes mellitus, the n0-STZ model, in which neonatal rats are injected with streptozotocin (STZ) at birth. METHODS: Following administration of ghrelin to n0-STZ rats from postnatal days 2 to 8, we examined beta cell mass, mRNA expression levels of insulin and of pancreatic and duodenal homeobox 1 (Pdx1) gene, and pancreatic morphology on days 21 and 70. In addition, we investigated the effects of ghrelin on beta cell replication. RESULTS: By day 21, ghrelin treatment increased pancreatic expression of insulin and Pdx1 mRNA in n0-STZ rats. The number of replicating cells was also significantly increased in the ghrelin-treated n0-STZ model. At day 70, n0-STZ rats exhibited hyperglycaemia, despite slight increases in plasma insulin levels. Ghrelin treatment resulted in the improvement of plasma glucose levels, which were associated with normal plasma insulin levels. Pancreatic insulin mRNA and protein levels were significantly increased in ghrelin-treated n0-STZ model animals. CONCLUSIONS/INTERPRETATION: These findings suggest that ghrelin promotes regeneration of beta cells in STZ-treated newborn rats. Thus, early administration of ghrelin may help prevent the development of diabetes in disease-prone subjects after beta cell destruction.

Aging↗
PubMed2006

Effects of mitiglinide on glucose-induced insulin release into the portal vein and fat-induced triglyceride elevation in prediabetic and diabetic OLETF rats.

OBJECTIVE: The effect of single-dose mitiglinide on glucose and lipid metabolism was examined in OLETF rats with spontaneous type 2 diabetes in which the early insulin response following glucose challenge is known to diminish over time and become lost with aging. METHODS: (1) With catheters inserted into the portal veins, 12-wk-old prediabetic OLETF rats were given an OGTT of 1 g/kg after 17 h of fasting. Eight rats each were orally given mitiglinide 1 mg/kg, nateglinide 50 mg/kg, or glibenclamide 1 mg/kg, vs 0.5% carboxymethylcellulose (CMC) as control, and were given an OGTT immediately afterward. Following oral administration of mitiglinide, nateglinide, glibenclamide, or 0.5% CMC, the 24-wk-old overt-diabetic OLETF rats were immediately given an OGTT of 1g/kg. (2) After 17 h of fasting, 24-wk-old OLETF rats were subjected to a fat-loading test. Eight rats each were given mitiglinide 3 mg/kg, glibenclamide 1 mg/kg, or glimepiride 1 mg/kg, vs 0.5% CMC, and were given soy oil 2 g/kg immediately afterward. They were also given mitiglinide orally and examined for LPL mRNA expression in their adipose tissue. RESULTS: (1) After OGTT, mitiglinide produced a significant increase in portal insulin levels 15 min after its administration, as well as a significant decrease in peripheral glucose levels 15-120 min after its administration in the OLETF rats. Likewise, nateglinide produced an increase in portal insulin levels and a decrease in peripheral glucose levels shortly after its administration in these rats. Glibenclamide increased portal insulin levels for an extended time after its administration, and significantly decreased peripheral glucose levels in the rats 120-300 min after its administration in the rats. In contrast, as in the 12-wk-old rats, a precipitous rise in insulin secretion was seen in the portal vein of 24-wk-old rats given mitiglinide, which peaked 15 min after mitiglinide administration, but the insulin levels continued to increase for 120 min or longer in the 24-wk-old rats given glibenclamide. In addition, as in the 12-wk-old rats, a significant decrease in glucose levels in peripheral blood was noted 30 and 60 min after mitiglinide administration and 300 min after glibenclamide administration in the 24-wk-old rats. (2) Mitiglinide increased LPL mRNA expression 120 min after its administration, and significantly decreased peripheral TG and chylomicron- TG levels after fat challenge in the 24-wk-old OLETF rats. CONCLUSION: Mitiglinide exhibited fast-onset and short-acting insulin-secretagogic effects, inhibiting post-glucose challenge increases in glucose levels and post-fat challenge increases in TG levels.

Adipose Tissue↗
PubMed2005

Collapse of coherent quasiparticle states in theta-(BEDT-TTF)2I3 observed by optical spectroscopy.

Optical conductivity measurements on the organic metal theta-(BEDT-TTF)2I3 revealed that the system crosses over rapidly from a coherent quasiparticle state to an incoherent state with temperature. Despite the metallic temperature dependence of resistivity, a well-defined Drude peak at low temperatures turns into a far-infrared peak with temperature. The peak energy shifts to higher frequencies and, simultaneously, the spectral weight is transferred to high frequencies beyond the electron band width. These characteristics imply that theta-(BEDT-TTF)2I3, so far believed to be a typical metal, is in fact a strongly correlated electron system with "bad-metal" character.

Electric Conductivity↗
PubMed2005

Increased visceral fat and impaired glucose tolerance predict the increased risk of metabolic syndrome in Japanese middle-aged men.

BACKGROUND: Impaired glucose tolerance (IGT) represents a stage of pre-diabetes and is a risk factor for future cardiovascular disease (CVD) which is a major cause of death in type 2 diabetes. The metabolic risk factors such as elevated blood pressure (elevated BP), abdominal obesity, dyslipidemia (elevated levels of total triglycerides [TG] and low levels of HDL cholesterol), and hyperglycemia precede the onset of the metabolic syndrome that increases the risk for CVD. This clustering is commonly associated with pre-diabetic hyperinsulinemia and it reflects peripheral insulin resistance. The present study documented that a visceral fat area (VFA) >/= 100 cm (2) can replace waist-to-hip ratios (WHR) associated with IGT or IFG/IGT as a critical risk for the development of the metabolic syndrome in Japanese middle-aged men. MATERIALS AND METHODS: A total of 575 middle-aged Japanese men with fasting plasma glucose levels of 6.1 - 6.9 mmol/l (impaired fasting glucose; IFG) were enrolled in the study. After a 75-g oral glucose tolerance test (OGTT), blood samples were collected 0 - 2 h later for determination of plasma glucose, insulin concentrations and other variables. Based on the results of an OGTT, the subjects were subgrouped into categories of glucose tolerance for further study. RESULTS: Subjects with IGT or IFG/IGT had significantly higher levels of metabolic abnormalities such as high BMI, increased AUC glucose, elevated HbA1c, high VFA, elevated BP, and increased TG levels when compared to NGT (normal glucose tolerance) (p < 0.001). Compensatory hyper-secretion of insulin was seen in all pre-diabetic subjects, and was higher in IFG/IGT subjects (681 +/- 33 pmol . h/l) than NGT (480 +/- 22 pmol . h/l) (p < 0.01). The metabolic clustering including abnormal VFA, TG, HDL-C, and BP was strongly associated with the development of metabolic syndrome. Interestingly, VFA >/= 100 cm (2) adjusted for the Japanese correlates strongly with the development of the metabolic syndrome in preclinical IGT or IFG/IGT subjects, with odds ratios of 2.7 and higher. CONCLUSION: VFA >/= 100 cm (2) strongly correlates with prediabetic IGT or IFG/IGT which is possibly associated with underlying insulin resistance, and is a critical risk factor linked to the development of metabolic syndrome in Japanese middle-aged subjects with IGT or IFG/IGT.

Adipose Tissue↗
PubMed2005

Weight loss-associated changes in acute effects of nateglinide on insulin secretion after glucose loading: results of glucose loading on 2 consecutive days.

AIM: The aim of this study was to investigate the influence of changes in insulin resistance and early insulin secretion on the insulin secretagogic effects of nateglinide. METHODS: Oral glucose tolerance testing (OGTT, 75 g) was performed in obese patients before and after weight loss on 2 consecutive days (first day OGTT without nateglinide, second day OGTT with nateglinide), to compare any weight loss associated changes in the nateglinide-induced insulin response to glucose loading. RESULTS: Reductions in visceral fat, liver fat, skeletal muscle fat and homeostasis model assessment (HOMA)-R due to weight loss were associated with increased Delta insulin 30 min/Delta glucose 30 min (DeltaI30/DeltaG30), and reduced area under the curve (AUC) for plasma glucose as seen in OGTT results. Results from OGTT showed that nateglinide administration was associated with reductions in plasma glucose AUC, both before and after weight loss. Before weight loss, although there was a significant elevation of DeltaI30/DeltaG30 associated with nateglinide treatment, no major change in the insulin-secreting dynamics after glucose loading was observed. After weight loss, nateglinide administration produced a significant increase in DeltaI30/DeltaG30, with insulin secretion peaking more quickly. CONCLUSION: Insulin response to nateglinide after glucose loading varied greatly in conjunction with weight loss. This may be accounted for not only by the enhancement of early insulin response to nateglinide associated with the improvement of early insulin response with weight loss but also by the reduced visceral fat, which in turn led to reduced levels of free fatty acids in portal blood and hepatic triglycerides, as well as increased hepatic insulin clearance.

Adipose Tissue↗
PubMed2005

Excess mortality in Black compared with White patients with Type 1 diabetes: an examination of underlying causes.

AIMS: Excess mortality in Type 1 diabetes has previously been found among Black individuals. The aim of the present study was therefore to determine underlying causes. METHODS: A longitudinal study of 1261 [1184 White (93.9%) and 76 Black (6.0%)] individuals diagnosed with Type 1 diabetes between 1965 and 1979, at age<17 years from the Allegheny County, Pennsylvania and Children's Hospital of Pittsburgh registries. Subjects were contacted in 1999 to determine living status and, where appropriate, cause of death. Living status was determined in 1183 participants (93.8%). RESULTS: Of the 200 deaths overall, cause of death was determined in 157 subjects (79%); 31 dying from acute and 101 from chronic complications, and 25 from non-diabetes related causes. Seven deaths were investigated but no cause determined. Black participants had a significantly higher mortality rate compared with White participants for acute complications (hazard ratio=4.9, 95% confidence interval: 2.0, 11.6), but not for any other cause. There was a temporal decline in the 20-year mortality rates in both racial groups across the three cohorts diagnosed in 1965-69, 1970-74 and 1975-79. CONCLUSIONS: These results show that the excess mortality in Black people was attributed to acute complications which therefore should be a focus for prevention.

Adolescent↗
PubMed2004

Role of early insulin secretion in postglucose-loading hyperglycaemia and postfat-loading hyperlipidaemia: comparing nateglinide and glibenclamide for acute effects on insulin secretion in OLETF rats.

AIM: The aim of this study was to clarify the role of an early insulin secretion in postprandial hyperglycaemia and hyperlipidaemia; a study using spontaneously type 2 diabetic Otsuka Long-Evans Tokushima Fatty rats with visceral obesity was performed to investigate the acute effect of nateglinide (NAT) vs. glibenclamide (GB) on increases in glucose after glucose loading and on increases in triglyceride (TG) after fat loading. METHODS: Fasting rats were given 50 mg/kg of NAT, 1 mg/kg of GB or 5% methyl cellulose (vehicle) as control and then immediately given oral glucose 1 g/kg. RESULTS: An acute increase in insulin levels in portal blood peaked at 15 min in the NAT group, while insulin levels in the GB group continued to increase significantly after 60 min. Glucose levels in peripheral blood were significantly lower in the NAT group at 30 and 60 min and in the GB group at 120, 180 and 270 min after glucose loading, compared with those in the vehicle group. Subsequently, fasting rats were given NAT, GB or vehicle and then immediately given oral fat emulsion (soy oil 2 g/kg). An acute increase in insulin secretion was seen with NAT, peaking at 30 min, while TG, chylomicron and very low-density lipoprotein levels after fat loading were shown to be significantly lower with NAT than with vehicle. However, the continued insulin secretion observed with GB led to no significant decrease in TG levels after fat loading. In addition, lipoprotein lipase mRNA expression in adipose tissue increased significantly 120 min after NAT administration in comparison with baseline. This increase was not noted with GB administration. CONCLUSION: Abnormalities in early insulin secretion are closely associated with the pathogenesis of various disease conditions that combine to characterize type 2 diabetes, suggesting that normalizing early insulin response in portal blood represents an important treatment not only for postprandial hyperglycaemia but also for postprandial hyperlipidaemia.

Adipose Tissue↗
PubMed2004

Comparison of the effects of glimepiride and glibenclamide on adipose tissue tumour necrosis factor-alpha mRNA expression and cellularity.

AIM: The aim of this study was to compare the effects of glimepiride and glibenclamide on tumour necrosis factor (TNF)-alpha expression and adipocyte cellularity in spontaneously diabetic, obese rats. METHODS: Eight-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats were randomized to receive glimepiride, glibenclamide or control treatment for 12 weeks, after which TNF-alpha mRNA levels, adipose tissue cellularity and physiological parameters were measured. RESULTS: TNF-alpha mRNA expression in retroperitoneal fat tissue was significantly greater in the glibenclamide group (2.2 +/- 1.1), compared with the control group (0.9 +/- 0.4; p<0.05) or the glimepiride group (0.9 +/- 0.2; p<0.01). The mean fat-cell area in retroperitoneal fat tissue was increased at study endpoint in the glibenclamide group (13,764 +/- 7036 microm2), compared with both the control and glimepiride groups (10,755 +/- 6193 microm2 and 11,317 +/- 5646 microm2 respectively; p<0.05). Investigation of cellularity revealed a decrease in the frequency of small fat cells and an increase in the frequency of large fat cells in both the glibenclamide and glimepiride groups compared with the control group, with a greater increase in large fat cells in the glibenclamide group. At study endpoint, insulin and triglyceride values were significantly higher in the active treatment groups compared with the control group; however, insulin levels were significantly greater in glibenclamide-treated animals compared with glimepiride-treated animals. An oral glucose tolerance test performed at the end of the study showed that there were no significant differences among the three groups in terms of plasma glucose and insulin concentrations. CONCLUSIONS: This study suggests that although both glibenclamide and glimepiride may have a hypertrophisizing effect on fat cells in adipose tissues, this effect is greater with glibenclamide, leading to augmentation of TNF-alpha mRNA expression and possible exacerbation of insulin resistance.

Adipose Tissue↗
PubMed2002

Adrenomedullin stimulates the growth of cultured normal human osteoblasts as an autocrine/paracine regulator.

Adrenomedullin (AM) is a 52 amino acid peptide that is synthesized in a variety of tissues, including the vessels and bones. This study showed that normal human osteoblast (NHOst) secreted immunoreactive AM and that AM stimulated intracellular cAMP production in these cells. An anti-AM monoclonal antibody, which inhibited endogenous AM, caused the number of NHOst to decrease. The effect of a low concentration AM was inhibited by addition of a cAMP-dependent protein kinase A inhibitor (H89). These data suggest that AM is an autocrine or paracrine regulator that promotes the proliferation of NHOst via the cAMP pathway.

Adrenomedullin↗
PubMed2001

Biochemical and morphological changes in herniated human intervertebral disc.

The molecular and morphologic features of herniated human intervertebral disc tissues are of particular importance to clarify the pathogenesis. The present study analyzed the biochemical and morphological features of herniated intervertebral disc tissues to determine the constituent factors responsible for intervertebral disc herniation. A total of 32 herniated disc specimens and 4 control disc samples were analyzed. Collagen subunit composition, collagenase activity, lipid peroxidation level, caspase-3 activity, metal levels, morphologic studies, and genetic analysis were performed on herniated disc tissues of chronic (group A) and acute (group B) group and compared with findings of control group. Nick translation analysis in situ revealed apoptotic-positive stained DNA fragments as black-brown spots in herniated disc tissues. The presence of type II collagen in control disc samples and its absence in herniated samples were confirmed immunohistochemically. The increased caspase-3 activity, the apoptotic-positive stained DNA fragments, and the electron microscopic findings suggest enhanced programmed cell death in herniated discs. The significant increase in lipid peroxidation levels and collagenase activity, and the low metal levels suggest the enhancement of cell death signals in herniated discs, caused by oxygen stress. Linkage analysis of herniated disc tissues in Japanese individuals may suggest ethnic variation. These findings may be helpful in understanding the pathogenesis of herniated disc disease.

Adolescent↗
PubMed2001

Troglitazone prevents the rise in visceral adiposity and improves fatty liver associated with sulfonylurea therapy--a randomized controlled trial.

Monotherapy with sulfonylurea may result in the exhaustion of pancreatic beta-cell function, fat accumulation, and dyslipidemia. We examined the possibility of dose reduction by administering sulfonylurea together with troglitazone, and investigated changes in insulin secretion and fat deposition. Seventy-eight patients with type 2 diabetes adequately controlled with glibenclamide were randomly allocated to a troglitazone (400 mg/d)-added group (n = 40) or a control group without placebo (n = 38) and monitored for 24 weeks. The daily dose of glibenclamide was adjusted to maintain stable HbA(1c) levels. Fat accumulation to the liver and thigh muscle were measured in mean Hounsfield units determined on computed tomography (CT) scan. Visceral fat accumulation (V), subcutaneous fat accumulation (S), and the V/S ratio were also determined by CT scan. The daily dose of glibenclamide and serum fasting insulin level in the troglitazone-added group significantly decreased (from 4.05 +/- 2.50 mg/d to 1.84 +/- 1.65 mg/d and from 8.47 +/- 4.62 microU/mL to 6.49 +/- 3.28 microU/mL, respectively) during the observation period compared with the control group (P < .01 and P < .01, respectively). Serum triglyceride and homeostasis model insulin resistance index (HOMA-R) in the troglitazone-added group decreased significantly in comparison to the control group (P < .05 and P < .01, respectively). The mean Hounsfield units of liver significantly decreased in the control group compared with the troglitazone-added group (P < .05). Visceral fat area and the V/S ratio significantly increased in the control group compared with the troglitazone-added group (P < .01 and P < .01, respectively). Glibenclamide monotherapy resulted in fat accumulation accompanied by dyslipidemia. An alternate conclusion is that troglitazone reversed type 2 diabetes (not sulfonylurea)-associated fat accumulation. The addition of troglitazone decreased daily doses of glibenclamide, preserved fasting insulin secretion, improved fat accumulation in liver, and prevented dyslipidemia.

Adipose Tissue↗
PubMed2001

Alcohol and the pancreas.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The presentations were (1) Phenotypic alteration of myofibroblast during ethanol-induced pancreatic injury: its relation to bFGF, by Masahiko Nakamura, Kanji Tsuchimoto, and Hiromasa Ishii; (2) Activation of pancreatic stellate cells in pancreatic fibrosis, by Paul S. Haber, Gregory W. Keogh, Minoti V. Apte, Corey S. Moran, Nancy L. Stewart, Darrell H.G. Crawford, Romano C. Pirola, Geoffrey W. McCaughan, Grant A. Ramm, and Jeremy S. Wilson; (3) Pancreatic blood flow and pancreatic enzyme secretion on acute ethanol infusion in anesthetized RAT, by H. Nishino, M. Kohno, R. Aizawa, and N. Tajima; (4) Genotype difference of alcohol-metabolizing enzymes in relation to chronic alcoholic pancreatitis between the alcoholic in the National Institute on Alcoholism and patients in other general hospitals in Japan, by K. Maruyama, H. Takahashi, S. Matsushita, K. Okuyama, A. Yokoyama, Y. Nakamura, K. Shirakura, and H. Ishii; and (5) Alcohol consumption and incidence of type 2 diabetes, by Katherine M. Conigrave, B. Frank Hu, Carlos A. Camargo Jr, Meir J. Stampfer, Walter C. Willett, and Eric B. Rimm.

Alcohol Drinking↗
PubMed2001

Descriptive epidemiology of male breast cancer in Osaka, Japan.

Male breast cancer is rare. The total number of incidence in Osaka for the period of 1966-95 was 182. Male-to-female ratio for breast cancer incidence was 1:164 in Osaka during this period. Mean age of the male breast cancer incidence was 63.3. The numbers of incidence and the crude incidence rates for male breast cancer have increased during the last 3 decades, while the age-standardized rates have remained constant. The age-specific incidence rates for males showed a gradual increase with age, while those for females showed a steep increase beginning at twenty years of age and a peak around 45-49 or 50-54 years old. The age-standardized incidence rates of male breast cancer were lower in Japan than in European countries and North America, as were those of female breast cancer. Distributions of the histological type and the extent of disease were not significantly different between males and females. Relative 5-year survival for the male breast cancer was, however, lower than that for the female, especially in the "regional" stage and "distant" stage. Further studies on the sex-difference in survival will be mandatory based on high-quality hospital cancer registries' data, which provide detailed information on the clinical stage and treatment.

Adolescent↗
PubMed2001

Mortality trends in type 1 diabetes. The Allegheny County (Pennsylvania) Registry 1965-1999.

OBJECTIVES: To investigate long-term mortality and its temporal trends as of 1 January 1999 among the 1,075 patients with type 1 diabetes (onset age <18 years, diagnosed between 1965 and 1979) who comprise the Allegheny County population-based registry. RESEARCH DESIGN AND METHODS: Overall, sex- and race-specific mortality rates per person-year of follow-up were determined. Standardized mortality ratios were also calculated. Survival analyses and Cox proportional hazard model were also used. Temporal trends were examined by dividing the cohort into three groups by year of diagnosis (1965-1969, 1970-1974, and 1975-1979). RESULTS: Living status of 972 cases was ascertained as of January 1, 1999 (ascertainment rate 90.4%). The mean duration of diabetes was 25.2 +/- 5.8 (SD) years. Overall, 170 deaths were observed. The crude mortality rate was 627 per 100,000 person-years (95% CI 532-728) and standardized mortality ratio was 519 (440-602). Life-table analyses by the Kaplan-Meier method indicated cumulative survival rates of 98.0% at 10 years, 92.1% at 20 years, and 79.6% at 30 years duration of diabetes. There was a significant improvement in the survival rate between the cohort diagnosed during 1965-1969 and that diagnosed during 1975-1979 by the log-rank test (P = 0.03). Mortality was higher in African-Americans than in Caucasians, but there were no differences seen by sex. The improvement in recent years was seen in both ethnic groups and sexes. CONCLUSIONS: An improvement in long-term survival was observed in the more recently diagnosed cohort. This improvement is consistent with the introduction of HbA1 testing, home blood glucose monitoring, and improved blood pressure therapy in the 1980s.

Adult↗
PubMed2001

Morphometric analysis of myelinated axons in the human vagus nerve.

Myelinated axons of the human vagus nerve were analyzed morphometrically on 30 cadavers (16 males and 14 females). The result showed that the transverse area and perimeter of myelinated axons decreased with age, although the total number of their axons did not change.

Adult↗