Toshiki Nakanishi

Hamamatsu University School Of Medicine, Hamamatu, Shizuoka, Japan

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Publications (14)31.24 Total impact

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    ABSTRACT: Background: Urinary myo-inositol (UMI) level is elevated in adult diabetic patients, and also increases after glucose loading. However, the relationship between UMI and plasma glucose levels in children is unknown. We aimed to assess whether UMI is a practical marker for glucose intolerance in children or not. Methods: In Study 1 (328 schoolchildren), fasting and postprandial UMI were measured, with ΔUMI defined as the difference between fasting and postprandial UMI levels. In Study 2, oral glucose tolerance tests and UMI measurements were conducted in 18 children with suspected having diabetes. Results: For Study 1, ΔUMI was observed [-0.65 (-3.9, 1.35) mg/g creatinine]. For Study 2, children with diabetes or impaired glucose tolerance had a significantly higher ΔUMI than children with normal glucose tolerance. Conclusion: These studies demonstrated the normal range of UMI in children and possibility of a novel biomarker for early detection of glucose intolerance in children.
    09/2015; DOI:10.1515/jpem-2015-0107
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    ABSTRACT: Context:Although AP2S1 has recently been shown to be a causative gene for familial hypocalciuric hypercalcemia type 3 (FHH3), knowledge about FHH3 remains poor.Objective:To report AP2S1 mutation and effects of low calcium formula in a patient with hypercalcemia and hypercalciuria.Patient:This Japanese female infant was found to have hypercalcemia by a routine laboratory test for poor weight gain on breast feeding. At 49 days of age, serum calcium (adjusted by Payne's formula) was 13.1 mg/dL, intact PTH 27 pg/mL, and urinary calcium to creatinine ratio 1.29 mg/mg. There was no evidence for hyperparathyroidism, PTHrP-producing neoplasm, and vitamin D excess. These data, except for hypercalciuria, appeared to be consistent with defective calcium-sensing receptor-mediated signaling. With use of low calcium formula containing 2.6 mg/dL of calcium, she showed catch-up growth, and serum calcium was decreased, as was urinary calcium to creatinine ratio. Furthermore, feeding with a mixture of low calcium formula and standard formula with a 2:1 ratio maintained serum calcium ∼12 mg/dL without markedly increasing serum PTH.Results:Although no pathologic mutation was detected in CASR or GNA11, a presumably de novo heterozygous mutation (p.Arg15Leu), a previously reported causative mutation for FHH3, was identified in AP2S1 of this patient.Conclusions:The results imply that lack of hypocalciuria does not necessarily argue against the presence of AP2S1 mutations. The early infantile age of this patient would have played a certain role in the occurrence of hypercalciuria, and low calcium formula is worth attempting in infants with FHH.
    The Journal of Clinical Endocrinology and Metabolism 09/2013; 98(12). DOI:10.1210/jc.2013-2571 · 6.21 Impact Factor
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    ABSTRACT: BACKGROUND: The prevalence of childhood obesity has increased worldwide over the past decade. Despite evidence that human milk lowers the risk of childhood obesity, the mechanism is not fully understood. AIMS: We investigated the direct effect of human milk on differentiation of 3T3-L1 preadipocytes. Study design and subjects: 3T3-L1 preadipocytes were treated with donated human milk only or the combination of the standard hormone mixture; insulin, dexamethasone (DEX), and 3-isobututyl-1-methylxanthine (IBMX). Furthermore, the induction of preadipocyte differentiation by extracted lipids from human milk was tested in comparison to the cells treated with lipid extracts from infant formula. Adipocyte differentiation, specific genes as well as formation of lipid droplets were examined. RESULTS: We clearly show that lipids present in human milk initiate 3T3-L1 preadipocyte differentiation. In contrast, this effect was not observed in response to lipids present in infant formula. The initiation of preadipocyte differentiation by human milk was enhanced by adding the adipogenic hormone, DEX or insulin. The expression of late adipocyte markers in Day 7 adipocytes that have been induced into differentiation with human milk lipid extracts was comparable to those in control cells initiated by a standard adipogenic hormone cocktail. CONCLUSIONS: These results demonstrate that human milk contains bioactive lipids that can initiate preadipocyte differentiation in the absence of the standard adipogenic compounds via a unique pathway.
    Early human development 06/2013; 89(9). DOI:10.1016/j.earlhumdev.2013.05.002 · 1.79 Impact Factor
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    ABSTRACT: Glucocorticoid (GC) excess promotes adipose tissue accumulation, and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays an important role in the local amplification of GC. Therefore, in this study, we investigated the effects of carbenoxolone (CBX), an 11β-HSD1 inhibitor, on morphological changes in visceral fat, and the expression of genes involved in adipogenesis and lipid metabolism in high-fat (HF) diet-fed mice. Mice were fed a HF diet from 5 weeks of age. At 10 weeks of age, the mice received an intraperitoneal injection of CBX or vehicle every day for 2 weeks. CBX decreased body weight and visceral fat mass, and improved insulin sensitivity in HF-fed mice. This was accompanied by reduced adipocyte size and a decrease in large-sized adipocytes in visceral fat. The expression of adipogenesis (PPARγ and C/EBPα), glucose transport (GLUT4) and lipid metabolism (LPL, ATGL, and HSL)-related genes were suppressed in CBX mice. CBX treatment induced beneficial morphological changes in visceral fat and decreased the expression of adipogenesis, glucose transport and lipid metabolism-related genes. These findings reveal a potential mechanism underling the effects of CBX on reduced fat accumulation and improved insulin sensitivity.
    Hormone and Metabolic Research 01/2012; 44(1):15-20. DOI:10.1055/s-0031-1297990 · 2.12 Impact Factor
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    ABSTRACT: Intrauterine growth restriction (IUGR) is associated with a substantially greater incidence of metabolic syndrome in adulthood. Animal studies have shown that IUGR offspring are hyperphagic during the early postnatal period and therefore exhibit obesity. The molecular mechanisms underlying food intake regulation in the gastrointestinal tract have not been clarified in IUGR. In the present study, we utilized a rat model of IUGR by restricting the food intake of the mother (50% of the normal intake, ad libitum; FR group) from day 7 of gestation until delivery. Pups from undernourished mothers were fostered by control mothers. We examined the food intake and assessed the gene expressions of ghrelin, peptide YY (PYY), and cholecystokinin (CCK) in the alimentary tract of male newborns (postnatal day1) and adult offspring (age, 7 months). Compared to the offspring whose mothers received the standard diet ad libitum (CON offspring), FR offspring were hyperphagic from the weaning time until the end of the experiment, and resulted in a heavier final weight. Both newborn and adult FR offspring had higher ghrelin gene expression in the stomach and higher ghrelin plasma levels than did the controls. Although the gastrointestinal gene expressions and plasma levels of the anorexic peptides, PYY and CCK, were elevated in the FR newborns, they decreased in the FR adults. Our findings suggest that the altered gene expressions of orexigenic and anorexigenic gut peptides in the gastrointestinal tract in the maternal undernutrition-induced IUGR offspring provide a potential mechanism to explain hyperphagia and obesity seen in these offspring.
    Hormone and Metabolic Research 03/2011; 43(3):178-82. DOI:10.1055/s-0030-1270528 · 2.12 Impact Factor
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    ABSTRACT: Kawasaki disease (KD) is a severe inflammatory disease that occurs in childhood. Recently, the initial corticosteroid therapy for KD has been reconsidered because its efficacy is controversial. The aim of this study was to evaluate the dynamic change in endogenous glucocorticoid levels and their relation with 11beta-hydroxysteroid dehydrogenase (11beta-HSD) activity in the acute phase of KD. Sixteen KD patients were investigated. Cortisol and cortisone levels, the cortisol/cortisone ratio and C-reactive protein (CRP) levels were measured on admission, before the first intravenous immunoglobulin (IVIG) therapy and convalescence. The 16 patients were divided into two groups. Group A included patients who received the first IVIG on admission and blood samples were collected before the first IVIG and convalescence. Group B included patients whose blood samples were collected at three different time points (on admission, before the first IVIG, and convalescence). CRP and cortisol levels and the cortisol/cortisol ratio were markedly higher before the first IVIG than those of convalescence in all patients except in one patient. In Group B patients, both serum cortisol levels and the cortisol/cortisone ratio on admission were significantly increased compared with those before the first IVIG (cortisol: p<0.005, cortisol/cortisone: p<0.001). Decreases in cortisol levels and the cortisol/cortisone ratio before the first IVIG may be explained by a reduction in adrenal secretion and/or local glucocorticoid action through 11beta-HSD activity. These findings suggest that exogenous glucocorticoid treatment in combination with the first IVIG at the acute stage may play a synergetic role in KD.
    Steroids 12/2010; 75(12):848-52. DOI:10.1016/j.steroids.2010.06.006 · 2.64 Impact Factor
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    ABSTRACT: Peroxisomal proliferator-activated receptors (PPARs) play an important role in the regulation of lipid metabolism. The aim of this study was to investigate the effects of a maternal high-fat (HF) diet on serum lipid concentration and PPAR gene expression in liver and adipose tissue in the early life of the rat offspring. Female Sprague-Dawley rats were fed either an HF or control (CON) diet 6 weeks before mating and throughout gestation and lactation. Blood and tissue samplings of male offspring were carried out at birth or weaning. Birth weights were similar and serum triglyceride (TG) and nonesterified fatty acid (NEFA) levels showed no significant difference between HF and CON newborns, despite greatly increased hepatic PPARα mRNA expression in the HF newborns (p<0.05). Both HF newborns and weanlings revealed significantly decreased hepatic PPARγ expression compared with controls (p<0.0001). Hepatic PPARα expression in the HF weanlings was reduced markedly compared with CON weanlings (p<0.0001) and showed a negative correlation with serum TG levels (r=-0.743, p<0.05). However, epididymal expression of PPARγ in the HF weanlings was upregulated significantly compared with controls (p<0.05) and demonstrated a positive correlation with epididymal fat mass (r=0.733, p<0.05). These were accompanied by obesity as well as a rise in serum TG by 79% (p<0.05) and NEFA concentration by 36% (p<0.05) in these HF weanlings. Our findings suggest that maternal HF diet leads to alterations in PPAR gene expression in the weanling offspring, which is associated with the disturbed lipid homeostasis.
    Hormone and Metabolic Research 10/2010; 42(11):821-5. DOI:10.1055/s-0030-1261954 · 2.12 Impact Factor
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    ABSTRACT: Antithyroid drugs are widely used in the therapy of Graves' disease (GD), and methimazole (MMI) is preferred for treatment of pediatric GD. The recommended initial dosage of MMI is 0.5-1.0 mg/kg/d for pediatric GD, although there are few studies on the optimal MMI dosage for initial treatment in children. We retrospectively compared the efficacy of different doses of MMI in 35 children with GD. Eight children were excluded due to lack of follow-up, etc. The remaining 27 children were divided into a high-dose group (HD; MMI≥0.7 (0.85 ± 0.13) mg/kg/d, n=8) and a low-dose group (LD; MMI<0.7 (0.51 ± 0.12) mg/kg/d, n=19), and we compared the time needed for the serum FT4 levels to normalize (≤1.6 ng/dl) between the groups. There were no significant differences between the FT4 levels (HD: 5.5 ± 2.8 ng/dl; LD: 5.0 ± 2.4 ng/dl p=0.59) or thyroid stimulating hormone receptor antibody levels (HD: 56.2 ± 29.3%; LD: 60.9 ± 27.2% p=0.69) between the groups before treatment. The mean time required to normalize the FT4 levels was 22.5 ± 7.4 d in the HD group and 28.8 ± 16.2 d in the LD group (p=0.30). In addition, no other factor influenced the time to efficacy of MMI. A dose of MMI<0.7 (0.51 ± 0.12) mg/kg/d appears to as effective as a higher dose in normalizing the serum FT4 level in children with mild or moderate GD.
    Clinical Pediatric Endocrinology 10/2010; 19(4):101-8. DOI:10.1297/cpe.19.101
  • R-S Li · Y Nakagawa · Y-J Liu · Y Fujisawa · S Sai · T Nakanishi · K E Chapman · J R Seckl · T Ohzeki
    Hormone and Metabolic Research 05/2008; 40(4):286-8. DOI:10.1055/s-2008-1058076 · 2.12 Impact Factor
  • Takehiko Ohzeki · Yuichi Nakagawa · Toshiki Nakanishi · Yasuko Fujisawa
    Nippon rinsho. Japanese journal of clinical medicine 01/2007; 64 Suppl 9:723-8.
  • Nippon rinsho. Japanese journal of clinical medicine 03/2005; 63 Suppl 2:345-8.
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    ABSTRACT: Tissue-specific dysregulation of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity in obese humans and animals may be associated with obesity and the metabolic syndrome. We investigated the effect of inhibition of 11beta-HSD with glycyrrhetinic acid (GE), an effective 11beta-HSD inhibitor, on body weight regulation in obese Zucker rats, which have a defect in the leptin receptor gene. GE (280 mg/kg/d) was administered in drinking water to 8-week-old male Zucker rats for 14 weeks. GE had no effect on food intake or weight gain, and did not affect hepatic 11beta-HSD1 and renal 11beta-HSD2 mRNA levels in obese rats. In contrast, average daily food intake and body weight on week 14 were significantly reduced by GE in lean rats (both P <.0001). Hepatic 11beta-HSD1 and renal 11beta-HSD2 mRNA levels were also significantly decreased by GE in lean rats (both P <.05). GE had no significant effect on plasma corticosterone levels in obese rats but lowered them in lean rats (P <.05). Plasma leptin levels declined in both GE-treated obese and lean rats (both P <.01). In conclusion, long-term GE treatment decreased weight gain in lean Zucker rats but not in obese Zucker rats. These findings suggest that the differing responses of 11beta-HSD1 to GE in obese and lean Zucker rats are closely associated with the different weight-gain responses. Furthermore, the weight-lowering effect of GE may require intact leptin receptors.
    Metabolism 06/2004; 53(5):600-6. DOI:10.1016/j.metabol.2003.11.010 · 3.89 Impact Factor
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    ABSTRACT: Mineralocorticoid hormones, which maintain electrolyte balance and blood pressure, are thought to be associated not only with the expression of renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), but also with that of intracellular mineralocorticoid receptors (MRs). The present study was designed to test whether the mineralocorticoid action of glucocorticoid corticosterone on renal MR is involved in the development of diabetes-associated hypertension by measuring the alterations of renal 11beta-HSD2. We measured the mean systolic blood pressure, renal 11beta-HSD1, and mRNA levels in streptozotocin (STZ)-induced diabetic rats that received spironolactone, insulin, or no treatment, and in nondiabetic controls that received spironolactone. Four weeks after an injection of STZ, the renal 11beta-HSD2 and mRNA levels were significantly lower in diabetic rats than in control rats, and the mean systolic blood pressure was 14.8% higher in diabetic rats than in controls. Subcutaneous injections of spironolactone into diabetic rats for three weeks partially reversed the decrease in renal 11beta-HSD2 activity and gene expression, and prevented the mean systolic blood pressure elevation. Spironolactone treatment for one week also resulted in a significant reduction in mean systolic blood pressure during the development of diabetic hypertension. However, treatment with STZ did not significantly decrease the renal 11beta-HSD1 activity and mRNA expression, and spironolactone treatment did not exert a significant effect on this enzyme in STZ-induced diabetic rats. In the development of diabetes-induced hypertension, the effect of spironolactone on mean systolic blood pressure may be associated with the mineralocorticoid effects of corticosterone on renal MR, as well as an alteration of renal 11beta-HSD2 activity and its mRNA expression in insulin-dependent diabetic rats.
    Kidney International 06/2000; 57(5):2064-71. DOI:10.1046/j.1523-1755.2000.00055.x · 8.56 Impact Factor
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    ABSTRACT: The present study describes a male neonate with an iliopsoas abscess. He was born by Caesarean section at 35 weeks and 3 days gestation. At 24-days-old he had a fever and localized swelling of the groin to the femur. By ultrasonography (US) and computed tomography (CT), the swelling was diagnosed as iliopsoas abscess. We treated him through percutaneous needle drainage and antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in the culture of the fluid from the abscess and the urine. US and CT were useful for the diagnosis and provided guidance for the needle puncture and follow-up of the iliopsoas abscess.
    Acta paediatrica Japonica; Overseas edition 09/1997; 39(4):459-61. DOI:10.1111/j.1442-200X.1997.tb03618.x

Publication Stats

62 Citations
31.24 Total Impact Points


  • 2008–2013
    • Hamamatsu University School Of Medicine
      Hamamatu, Shizuoka, Japan
  • 2004–2013
    • Hamamatsu University School of Medicine
      • Department of Pediatrics
      Hamamatu, Shizuoka, Japan
  • 2000–2005
    • Tokoha University
      • Department of Pediatrics
      Hamamatu, Shizuoka, Japan
  • 1997
    • Haibara General Hospital
      Hagihara, Nara, Japan