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Biomedical subjects

S Nagasaka

Publications and source records attributed to S Nagasaka.

At least 19 recordsLinked to original sources
PubMed2006

Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control.

AIMS/HYPOTHESIS: Hyperlipidaemia often occurs in patients with type 2 diabetes mellitus. Though HMG-CoA reductase inhibitors (statins) are widely used for controlling hypercholesterolemia, atorvastatin has also been reported to have an adverse effect on glucose metabolism. Based on these findings, the aim of this study was to investigate the effects of statins on adipocytes, which play pivotal roles in glucose metabolism. METHODS: In 3T3-L1 cells, effects of statins on adipocyte maturation were determined morphologically. Protein and mRNA levels of SLC2A4 and adipocyte marker proteins were determined by immunoblotting and RT-PCR, respectively. Type 2 diabetic NSY mice were treated with atorvastatin for 15 weeks, followed by glucose and insulin tolerance tests and examination of SLC2A4 expression in white adipose tissue (WAT). Seventy-eight Japanese subjects with type 2 diabetes and hypercholesterolaemia were treated with atorvastatin (10 mg/day), and its effects on lipid and glycaemic profiles were measured 12 weeks after treatment initiation. RESULTS: Treatment with atorvastatin inhibited adipocyte maturation, SLC2A4 and C/EBPalpha expressions and insulin action in 3T3-L1 cells. Atorvastatin also attenuated SLC2A4 and C/EBPalpha expressions in differentiated 3T3-L1 adipocytes. These effects were reversed by L. mevalonate or geranylgeranyl pyrophosphate. In NSY mice, atorvastatin accelerated glucose intolerance as a result of insulin resistance and decreased SLC2A4 expression in WAT. In addition to improving hyperlipidaemia, atorvastatin treatment significantly increased HbA(1c) but not fasting glucose levels in diabetic patients, and this effect was greater in the non-obese subgroup. CONCLUSIONS/INTERPRETATION: These results demonstrate that atorvastatin attenuates adipocyte maturation and SLC2A4 expression by inhibiting isoprenoid biosynthesis, and impairs glucose tolerance. These actions of atorvastatin could potentially affect the control of type 2 diabetes.

3T3 Cells↗
PubMed2006

Early onset insulin-dependent diabetes mellitus as an initial manifestation of aceruloplasminaemia.

BACKGROUND: Aceruloplasminaemia is an autosomal recessive disorder caused by specific mutations in the ceruloplasmin gene. Aceruloplasminaemia is clinically characterized by diabetes mellitus, pigment degeneration of the retina, and neurological abnormalities, such as cerebellar ataxia, extrapyramidal signs, and dementia. We present a patient with aceruloplasminaemia who, until progressive neurological abnormalities were noticed, had been treated for more than 30 years as having Type 1 diabetes mellitus requiring multiple insulin injection therapy. CASE REPORT: The patient was a 58-year-old man. At the age of 23 years, he developed diabetes that required multiple insulin injection therapy. At the age of 39 years, he was commenced on continuous subcutaneous insulin infusion (CSII) therapy. Despite CSII therapy, the patient's blood glucose levels were poorly controlled (HbA(1c), approximately 9.5%). He was diagnosed as having aceruloplasminaemia at 58 years of age when he presented with progressive cerebellar ataxia, extrapyramidal signs of recent onset and pigment degeneration of the retina. CONCLUSIONS: It is possible that some diabetic patients with aceruloplasminaemia are mistakenly diagnosed as having Type 1 diabetes mellitus, as they have reduced insulin secretion and develop diabetes at a younger age, before neurological abnormalities associated with aceruloplasminaemia are apparent. Therefore, aceruloplasminaemia should be considered in patients with insulin-dependent diabetes mellitus who develop progressive neurological abnormalities of unknown aetiology along with a microcytic hypochromic anaemia and retinal degeneration.

Blood Protein Disorders↗
PubMed2005

Soluble TNF receptors and albuminuria in non-obese Japanese type 2 diabetic patients.

The aim of this study was to investigate the relationships between albuminuria and tumor necrosis factor (TNF)-alpha or soluble TNF receptors (sTNF-R1, sTNF-R2) in eighty-eight non-obese Japanese type 2 diabetic patients stratified into two groups according to albuminuria status-microalbuminuria or normoalbuminuria. Patients with microalbuminuria were older and had significantly higher concentrations of sTNF-R1 and sTNF-R2 than those with normoalbuminuria. There was, however, no significant difference in sex, diabetes duration, smoking, BMI, systolic and diastolic blood pressure, HbA (1c), serum creatinine, and lipid profile between the two groups. Although serum TNF-alpha was positively correlated to serum sTNF-R1 and sTNF-R2, serum TNF-alpha level did not differ with respect to albuminuria. Univariate regression analysis showed that urinary albumin concentration was positively correlated to age (r=0.380, p<0.001), serum creatinine (r=0.214, p<0.05) and concentrations of sTNF-R1 (r=0.364, p<0.001) and sTNF-R2 (r=0.342, p<0.005). Other variables, including TNF-alpha, were not associated with albuminuria. Multiple regression analyses showed that urinary albumin concentration was independently predicted by the level of sTNF-R1 (F=32.1), which explained 26.3% of the variability of urinary albumin concentration. From these results, it can be concluded that serum soluble TNF receptor is an important independent factor associated with albuminuria in non-obese Japanese type 2 diabetic patients.

Aged↗
PubMed2004

Xenogeneic embryonic stem cell-derived cardiomyocyte transplantation.

PURPOSE: The purpose of this study was to investigate the survival of xenogeneic embryonic stem cell (ES cell)-derived cardiomyocytes transplanted into the normal myocardium. MATERIAL AND METHODS: Undifferentiated mouse ES cells carrying the enhanced green fluorescent protein (EGFP) were cultured in hanging drops and then plated onto dishes. These cells were identified as cardiomyocytes by the expression of cardiac-specific genes, recording of action potential, and immunostaining with anti-sarcomeric myosin antibody. Donor cells were injected into the normal myocardium, with cyclosporine administered daily. One week after the transplantation, we investigated donor cell survival by examining EGFP expression, hematoxylin and eosin staining, and immunostaining with anti-sarcomeric myosin antibody. RESULTS: In vitro donor cells derived from ES cells expressed myosin light chain-2v and alpha-myosin heavy chain genes, had action potentials of a ventricular myocyte type, and were stained by anti-sarcomeric myosin antibody. In vivo 1 week after transplantation, EGFP-expressed cells were detected in the cell transplanted area. No lymphocytic infiltration was observed around these cells. CONCLUSIONS: ES cell-derived cardiomyocytes survived in the normal myocardium after the transplantation, even in a discordant xenogeneic transplantation model. These results indicate that cell transplantation using cardiomyocytes derived from ES cells, even if xenogeneic represents an attractive strategy for treating heart disease.

Action Potentials↗
PubMed2004

Relationship between immunological rejection and matrix GLA protein in cryopreserved vascular allografts.

INTRODUCTION: Cryopreserved tissue allografts used for cardiovascular diseases become calcified as a late complication after transplantation, probably caused by immunological rejection. Recent attention has been focused on the inhibitory effect of matrix Gla protein (MGP) on ectopic vascular calcification, but the behavior of MGP in cryopreserved allografts is uncertain. In this study we examined the relationship between immunological rejection and MGP in cryopreserved rat aortic grafts after transplantation. METHODS: Cryopreserved rat aortae were isografted or allografted intraperitoneally. Fresh isografts were also tested. The grafts were retrieved 9 days after transplantation and the intragraft MGP mRNA was measured by a real-time quantitative PCR method. The effect of daily administration of FK506 on MGP mRNA levels in cryopreserved isografts and allografts after transplantation was also evaluated. RESULTS: There was no significant difference in intragraft MGP mRNA levels between fresh and cryopreserved isografts 9 days after transplantation. MGP expression levels in cryopreserved allografts were significantly lower as compared to those in cryopreserved isografts (P < .01). Daily administration of FK506 enhanced intragraft MGP mRNA (ninefold) in cryopreserved allografts (P < .01), but not in cryopreserved isografts. CONCLUSIONS: Immunological rejection is likely to inhibit MGP expression in cryopreserved vascular allografts, resulting in late-onset calcification.

Animals↗
PubMed2004

Prevalence of periodontal bacterial infection in non-obese Japanese type 2 diabetic patients: relationship with C-reactive protein and albuminuria.

The aim of the present study was to investigate the relationship between periodontal bacteria infection ( Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedius) and C-reactive protein (CRP) and albuminuria in non-obese Japanese type 2 diabetic patients. One hundred and thirty-four non-obese Japanese type 2 diabetic patients without evidence of current acute illness including clinically significant acute infectious disease were enrolled into the study. The degree of periodontal bacterial infection was evaluated using IgG titer against Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, or Prevotella intermedius. The bacterial sonic extracts were used as antigens. High-sensitivity CRP (hCRP), glucose, glycosylated hemoglobin (HbA (1c)), and lipids were also measured after an overnight fast. Urinary albumin excretion rate as a ratio of urinary albumin and urinary creatinine was assessed in a morning spot urine sample using a commercial enzymatic immunoassay. The prevalence of Porphyromonas gingivalis infection was 52.2 % and that of Actinobacillus actinomycetemcomitans and Prevotella intermedius was 7.5 and 14.2 %, respectively. IgG titer against Porphyromonas gingivalis significantly correlated with CRP (r = 0.225, p < 0.001) and albuminuria (r = 0.185, p < 0.05), while IgG titer against Actinobacillus actinomycetemcomitans or Prevotella intermedius was not associated with either parameter. These results suggest that among periodontal bacteria, Porphyromonas gingivalis infection is associated with atherosclerosis in non-obese Japanese type 2 diabetic patients.

Actinobacillus Infections↗
PubMed2004

Comparison of pioglitazone and metformin efficacy using homeostasis model assessment.

AIMS: To compare clinical efficacy of two different insulin sensitizers, pioglitazone and metformin, and to reveal factors that influence the clinical efficacy. METHODS: Seventy-eight Japanese subjects with Type 2 diabetes mellitus poorly controlled with sulphonylureas [38 men and 40 women, aged 57 +/- 9 years, body mass index 25.2 +/- 1.4 kg/m2, and HbA1c 8.3 +/- 0.6% (means +/- SD)] were randomly assigned to groups for the addition of either pioglitazone or metformin and followed up for 4 months. A decrease in HbA1c levels was compared with baseline factors including homeostasis model assessment of insulin sensitivity (HOMA-R) and beta-cell function (HOMA-beta) with 71 subjects who completed the study. RESULTS: The overall decrease in HbA1c levels was similar for the pioglitazone (-1.2 +/- 0.2%) and metformin (-1.3 +/- 0.1%) groups. In the pioglitazone group, the decrease in HbA1c levels was negatively correlated with baseline HOMA-R (r=-0.698, P<0.0001) and HOMA-beta (r=-0.680, P<0.0001). In contrast, the decrease was positively correlated with baseline HOMA-beta (r=0.556, P=0.0004) in the metformin group. Multivariate analysis revealed that either HOMA-R or HOMA-beta was a main determinant of the decrease in HbA1c levels in the pioglitazone group. In the metformin group, baseline levels of fasting glucose were also included as an independent determinant in addition to HOMA-beta. The subjects with greater HOMA-R (> or =4.0) or HOMA-beta (> or =40%) displayed better response to pioglitazone than to metformin, and vice versa. CONCLUSIONS: In Type 2 diabetic subjects poorly controlled with sulphonylureas, addition of pioglitazone or metformin resulted in a comparable reduction in HbA1c levels. Subjects with greater insulin resistance or preserved beta-cell function displayed better response to pioglitazone, whereas subjects with reduced beta-cell function displayed better response to metformin.

Diabetes Mellitus, Type 2↗
PubMed2003

Relationship of regional adiposity to serum leptin level in nonobese Japanese type 2 diabetic male patients.

BACKGROUND: The aim of the present study was to investigate the relationships between serum leptin levels and regional adipose fat area, BMI, and the measures of variables including serum insulin in nonobese Japanese type 2 diabetic patients. METHODS: A total of 121 nonobese Japanese type 2 diabetic patients [aged 35 to 83 years, body mass index (BMI) (15.4 to 26.8 kg/m(2))] were studied. They all were male patients. In conjunction with serum leptin level, BMI, glycosylated hemoglobin (HbA(1c)), and fasting concentrations of plasma glucose and serum insulin and lipids (triglycerides, total and HDL cholesterol) were measured. RESULTS: Univariate regression analysis showed that serum leptin levels were positively correlated to subcutaneous (r=0.566, P<0.0001) and visceral (r=0.481, P<0.001) fat area in our diabetic patients. Furthermore, serum leptin levels were positively correlated to serum insulin (r=0.517, P<0.0001), BMI (r=0.428, P<0.0001), serum triglycerides (r=0.279, P<0.005), and age (r=0.225, P<0.05). There was, however, no relationship between serum leptin levels and measures of other variables including total and HDL cholesterol. Multiple regression analyses showed that serum leptin levels were predicted by subcutaneous fat area (F=5.92, P<0.0001) and serum insulin level (F=5.60, P<0.0001), which explained 29.0% of the variability of serum leptin concentrations in our nonobese Japanese type 2 diabetic male patients. Visceral fat area, BMI, serum triglycerides, and age, however, were not independently associated with serum leptin levels in our patients. CONCLUSIONS: These results indicate that serum leptin levels are reflective of subcutaneous fat area in nonobese Japanese type 2 diabetic male patients.

Adipose Tissue↗
PubMed2003

"All in one" cardiopulmonary bypass circuit for aortic surgery.

We devised an "all in one" cardiopulmonary bypass circuit for aortic surgery, and evaluated its efficacy and safety. The circuit consisted of a venous line, reservoir, single centrifugal pump, membrane oxygenator and arterial line bifurcated into two lines for systemic perfusion and selective branch perfusion. The perfusion volume was regulated by an occluder and measured by a flow sensor. A closed partial bypass was established using a shunt line bypassing the reservoir. We applied this circuit to 25 patients with aortic disease. Regulation of both the selective cerebral perfusion (SCP) and the selective branch perfusion was easily performed. There was neither stroke nor organ dysfunction postoperatively. There are some cases in which it is difficult to decide the necessity for SCP preoperatively; the use of this circuit may resolve this problem. This circuit can be easily and safely applied to any type of aortic surgery.

Adult↗
PubMed2002

Effect of short-term low-intensity exercise on insulin sensitivity, insulin secretion, and glucose and lipid metabolism in non-obese Japanese type 2 diabetic patients.

The aim of the present study was to investigate the effects of short-term physical exercise that did not change body mass on insulin sensitivity, insulin secretion, and glucose and lipid metabolism in 39 non-obese Japanese type 2 diabetic patients. Insulin sensitivity and insulin secretion were estimated with homeostasis model assessment insulin resistance (HOMA-IR) and HOMA-B-cell function proposed by Matthews et al., respectively. All patients were hospitalized and were engaged in low-intensity exercise that consisted of walking and dumbbell exercise for successive 7 days. There were no changes in hospital diet and the dose of any medications used throughout the study. Fasting glucose, insulin, and lipids were measured before and after exercise. After exercise, serum triglyceride levels significantly decreased, but no significant changes were observed in total and HDL cholesterol concentrations. Fasting glucose, insulin, and HOMA-IR levels significantly decreased after exercise, but HOMA-B-cell function did not change during the study. There was no significant difference between BMI levels before and after exercise. From these results, it can be concluded that short-term (7 days) low-intensity physical exercise combined with hospital diet reduces serum triglycerides, insulin resistance, and fasting glucose levels without affecting BMI in non-obese Japanese type 2 diabetic patients.

Adult↗
PubMed2001

Arginine vasopressin inhibits apoptosis of rat glomerular mesangial cells via V1a receptors.

Arginine vasopressin (AVP) promotes proliferation of glomerular mesangial cells. We examined whether AVP modulates an apoptosis of cultured rat glomerular mesangial cells at 3-17th passages. The agarose gel electrophoresis demonstrated that AVP attenuated a ladder formation stimulated by the serum deprivation. The quantitation of oligonucleosomes by ELISA also showed that AVP suppressed the serum deprivation-induced apoptosis. Such an antiapoptotic effect of AVP was dose-dependent. An AVP V1a receptor antagonist, d(CH2)5Tyr(Me)AVP, abolished the antiapoptotic effect of AVP. The inhibitory effect of AVP on the apoptosis was reduced by staurosporine and mimicked by phorbol-12-myristate-13-acetate. These results suggest that AVP inhibits serum deprivation-induced apoptosis of glomerular mesangial cells via V1a receptor-protein kinase C pathway.

Animals↗
PubMed2001

Urinary excretion of the aquaporin-2 water channel exaggerated in pathological states of impaired water excretion.

OBJECTIVE: The present study was undertaken to determine whether the hydro-osmotic action of arginine vasopressin (AVP) is exaggerated in pathological states of impaired water excretion by measuring urinary excretion of the aquaporin-2 (AQP-2) water channel. PATIENTS AND MEASUREMENTS: Eighteen hyponatraemic patients with impaired water excretion and 12 control subjects were studied during an acute oral water load (20 ml/kg body weight). RESULTS: In the patient group plasma AVP levels were 1.6 pmol/l, relatively high compared to plasma osmolality of 279.8 mmol/kg. Urinary excretion of AQP-2 under ad libitum water drinking was 41.1 fmol/micromol creatinine in the patient group, a value significantly greater than that of 21.7 fmol/micromol creatinine in the control subjects. The acute water load verified the impairment in water excretion in the patient group, as the excretion of the water load was only 28.2% (control, 77.3%, P < 0.001) and the minimum urinary osmolality was as high as 437.3 mmol/kg (control, 122.9 mmol/kg, P < 0.001). Also, the minimum urinary excretion of AQP-2 was significantly greater in the patient group than that in the control. There was a positive correlation between plasma AVP levels and urinary excretion of AQP-2 in the control subjects (r = 0.56, P < 0.01). In contrast, the urinary excretion of AQP-2 was exaggerated compared to the respective plasma AVP levels in the patient group, and thus the positive correlation disappeared. CONCLUSION: These results indicate that hydroosmotic action of AVP is exaggerated more than that expected from plasma AVP levels in pathological states of impaired water excretion, with non-suppressible, but normal, arginine vasopressin levels in spite of the hypo-osmotic condition.

Aged↗