Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
最新号
選択された号の論文の12件中1~12を表示しています
REVIEW
  • Junta Imai
    原稿種別: Review
    2018 年 65 巻 7 号 p. 677-684
    発行日: 2018年
    公開日: 2018/07/28
    [早期公開] 公開日: 2018/07/03
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    In insulin-resistant states such as obesity, pancreatic β-cells proliferate to prevent blood glucose elevations. However, the mechanism(s) by which obesity induces compensatory β-cell responses is not fully understood. Recently, several studies have shown that signals from the liver, such as neuronal signals or humoral factors, regulate β-cell proliferation during obesity development. We previously reported a liver-brain-pancreas neuronal relay, consisting of afferent splanchnic nerves, the central nervous system and efferent vagal nerves, to promote this compensatory β-cell proliferation. Furthermore, we recently clarified the molecular mechanisms by which efferent vagal signals induce β-cell proliferation in this inter-organ neuronal network system. Herein, these liver-β-cell inter-organ networks are reviewed, focusing mainly on the neuronal network. The significance of the neuronal network system in the maintenance of glucose homeostasis is also discussed with reference to the relevant literature.

ORIGINAL
  • Huanhuan Zang, Fusong Jiang, Xingbo Cheng, Hong Xu, Xingna Hu
    原稿種別: Original
    2018 年 65 巻 7 号 p. 685-691
    発行日: 2018年
    公開日: 2018/07/28
    [早期公開] 公開日: 2018/04/17
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    Adropin has been identified as potent regulatory hormone implicated in insulin sensitivity and the maintenance of energy homeostasis. The aim of current study was to investigate serum adropin concentrations of type 2 diabetes mellitus (T2DM) patients in the fasting status, especially those overweight/obese and evaluate the relationships between adropin levels and metabolic parameters. A total of 116 T2DM patients and 60 controls with normal glucose tolerance (NGT) were recruited to the study. Adropin concentration was determined using commercial ELISA kits. Anthropometric characteristics were collected and biochemistry, glycosylated hemoglobin A1c (HbA1c) and fasting insulin (FIns) were detected by clinical laboratory. Insulin resistance was estimated by homeostasis model 2 assessment of insulin resistance (HOMA2-IR). Serum adropin levels in Chinese T2DM patients were decreased compared with the controls [3.8 (3.0–5.5) vs. 5.5 (3.7–7.9) ng/mL, p < 0.01]. Meanwhile, overweight/obese patients had more considerably reduced levels of adropin. Adropin level was negatively correlated with body mass index (BMI), high-sensitive C reactive protein (hs-CRP), triglycerides (TG), fasting plasma glucose (FPG), FIns, HOMA2-IR and HbA1c, while positively with high-density lipoprotein cholesterol (HDL-C) in study participants (p < 0.01). The correlations of adropin with glucolipid variables (TG, HDL-C, FPG, FIns, HOMA2-IR, HbA1c) still existed after adjusting the effect of BMI. Besides, HOMA2-IR and HbA1c were independent factors associated with serum adropin levels. Binary logistic regression analyses showed that adropin was significantly associated with T2DM after removing confounding factors (p < 0.01). Receiver operating characteristic (ROC) curve demonstrated adropin concentration of 5.8 ng/mL could be used as a possible optimal cut-off value to identify T2DM from non-T2DM with sensitivity of 81.9% and specificity of 46.7%. Serum adropin concentrations are decreased in Chinese T2DM patients, especially those overweight/obese. Adropin, associated with glucolipid homeostasis and insulin sensitivity, may implicate in the pathogenesis of T2DM.

  • Atsunori Kashiwagi, Taishi Sakatani, Ichiro Nakamura, Noriko Akiyama, ...
    原稿種別: Original
    2018 年 65 巻 7 号 p. 693-705
    発行日: 2018年
    公開日: 2018/07/28
    [早期公開] 公開日: 2018/05/29
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    To examine differential improvements among cardiovascular risk factors in response to treatment with ipragliflozin in Japanese type 2 diabetes mellitus (T2DM) patients, we conducted a pooled analysis of six randomized, double-blind trials of Japanese T2DM patients who received ipragliflozin 50 mg/day or placebo and had patient-level data for cardiometabolic risk parameters. Risk factors included glycated hemoglobin (HbA1c), body weight, homeostatic model assessment for insulin resistance and beta-cell function (HOMA-R and HOMA-beta, respectively), systolic blood pressure, fasting serum insulin concentrations, and the concentration of uric acid, lipids, and liver enzymes from baseline to end of treatment (EOT; 12–24 weeks). The primary endpoint of each trial was the change in HbA1c from baseline to EOT. Changes in risk factors from baseline to EOT were compared between ipragliflozin-treated and placebo groups, and between two subgroups (high- and low-risk groups for each parameter). All parameters, except low-density lipoprotein cholesterol (LDL-C) and non high-density lipoprotein cholesterol (non HDL-C), improved significantly in the ipragliflozin group. Subgroup analysis revealed a significantly greater improvement in the high-risk group versus low-risk group in HbA1c, HOMA-R, HOMA-beta, aspartate transaminase, alanine transaminase, and gamma-glutamyltransferase, but not in any of the lipid parameters or blood pressure. Liver function improvement in the ipragliflozin group was significantly correlated with changes in body weight, HbA1c, HOMA-beta, and HOMA-R. This analysis demonstrated that, in Japanese T2DM patients, ipragliflozin 50 mg/day was associated with improvements in cardiometabolic risk factors, except for LDL-C and non HDL-C.

  • Yasuhiro Ito, Akira Miyauchi, Mitsuyoshi Hirokawa, Masatoshi Yamamoto, ...
    原稿種別: Original
    2018 年 65 巻 7 号 p. 707-716
    発行日: 2018年
    公開日: 2018/07/28
    [早期公開] 公開日: 2018/04/20
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    The tumor-node-metastasis (TNM) staging system is most commonly adopted to evaluate the prognosis of patients with thyroid carcinoma. The 8th edition of the TNM staging system, an extensively revised version of the 7th edition, was recently released. We aimed to investigate whether and how well the 8th edition reflects the cause-specific survival (CSS) of patients with papillary thyroid carcinoma by analyzing the cases in 5,892 patients who underwent initial surgery at Kuma Hospital between 1987 and 2005. The median postoperative follow-up duration was 178 months (range: 6–357 months). One patient with T4b disease was excluded from the analysis. Overall, 116 (2.0%) patients died of thyroid carcinoma. The proportion of variance explained (PVE) for CSS in the 7th and 8th editions was 10.69 and 10.97, respectively. Using the 7th edition, CSS of patients with stage IVA and stage III disease was similar (p = 0.32). In contrast, using the 8th edition, CSS was poorer in stage II than in stage I (p < 0.001), in stage III than in stage II (p < 0.001), and in stage IVB than in stage III (p < 0.001). Similar results were observed for disease-free survival. Although we could not establish any objective evidence that the 8th edition is superior to the 7th edition, the 8th edition is simpler and more convenient, as it includes fewer stages and addresses the issue of the 7th edition where stage IVA and III patients had similar prognoses.

  • Min Chen, Chang Chen, Xiaohui Yuan, Xiaoqi Chen, Feng Zheng, Liang Sha ...
    原稿種別: Original
    2018 年 65 巻 7 号 p. 717-725
    発行日: 2018年
    公開日: 2018/07/28
    [早期公開] 公開日: 2018/04/28
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    Lung infection is one of the most common infections in diabetes mellitus and is characterized by increased pulmonary microvascular endothelial permeability. Local Angiotensin II (AngII) plays an important role in the pathogenesis of lung diseases. However, whether AngII can aggravate diabetic infectious lung injury is not clear. Therefore, we investigated the effects of AngII on the permeability of human pulmonary microvascular endothelial cells (HPMVECs) challenged by lipopolysaccharide (LPS) in high glucose states in vitro. HPMVECs were divided into five groups: a control group (CON), a high glucose group (HG), an LPS + high glucose group (LH), an LPS + high glucose + AngII group (LHA), and an LPS + high glucose + Losartan group (LHL). The HPMVECs permeability as well as the F-actin levels, cytoskeleton, apoptosis and TNF-α concentrations were evaluated. Compared to the CON group, the HG, LH and LHA groups had significantly higher cellular permeability, cellular apoptosis and TNF-α levels, with more extensive cytoskeletal damage and lower F-actin levels. Additionally, cells in the LHA group exhibited significantly elevated permeability, apoptosis and TNF-α concentrations, lower F-actin levels and more extensive cytoskeletal damage than either the LH or HG group. However, compared to the HG or LH group, the LHL group showed significantly lower cellular permeability, cell apoptosis, cytoskeletal damage and TNF-α concentrations and higher F-actin levels. This study suggests that in a diabetic infectious lung injury cellular model, AngII could aggravate the permeability of HPMVEC via F-actin dynamics and cell apoptosis. Furthermore, blocking the Angiotension II Type 1 Receptor could significantly alleviate the hyperpermeability of HPMVECs.

  • Ying Guo, Zhonghou Han, Li Guo, Yu Liu, Gang Li, Huiqing Li, Jie Zhang ...
    原稿種別: Original
    2018 年 65 巻 7 号 p. 727-735
    発行日: 2018年
    公開日: 2018/07/28
    [早期公開] 公開日: 2018/05/12
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    Gestational Diabetes Mellitus (GDM) has brought great harm to maternal and fetus. Up to now, only a few plasma biomarkers for its early diagnosis have been reported; nevertheless, there is no report about identification of urinary biomarkers for prediction of GDM. Thus, it is necessary to correct this deficiency. In our study, urine samples were collected from 889 healthy young gravidae at the early second trimester (15 to 20 weeks), 69 of whom were subsequently diagnosed with GDM at 24 to 28 weeks. iTRAQ (the isobaric tags for relative and absolute quantification) quantitative proteomics was conducted on sixteen GDM (trial group) and an equal number of matched healthy young gravidae (control group). Validation was performed in 40 cases of each group by ELISA. A total of 1,901 proteins were identified in this study, including 119 significantly differential proteins (fold change ≧1.2 or ≦0.83 and p < 0.05). Compared with control group, 83 differential proteins were increased and 36 proteins were decreased in GDM group. The validation for expression of CD59 and IL1RA showed significant difference and the area under the receiver operating characteristic curve was 0.729 and 0.899, respectively (p < 0.05). The two candidate protein biomarkers (CD59 and IL1RA) in urine could be an early, noninvasive diagnostic predictors of young pravidae with GDM, and IL1RA is stronger diagnostic power than CD59.

  • Hideyuki Okuma, Koshi Hashimoto, Takuya Ohashi, Masatomo Mihara, Isao ...
    原稿種別: Original
    2018 年 65 巻 7 号 p. 737-746
    発行日: 2018年
    公開日: 2018/07/28
    [早期公開] 公開日: 2018/04/26
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    A 29-year-old man was referred to our department due to adrenal insufficiency with the inappropriate secretion of TSH (SITSH). Magnetic resonance imaging revealed a pituitary tumor. A weak TSH response in the TRH test, elevated sex hormone binding globulin (SHBG) levels, and the absence of a family medical history of SITSH or TRβ gene mutations supported the diagnosis of TSH-secreting pituitary adenoma (TSHoma). However, complete TSH suppression and a blunted cholesterol response in the T3 suppression test as well as normal glycoprotein α-subunit (α-GSU) levels were not compatible with TSHoma. Since TSH, FT3, and FT4 spontaneously returned to normal ranges after admission, he was discharged. One month after his discharge, thyrotoxicosis with elevated serum TSH levels relapsed. After admission, his serum TSH levels returned to within the normal range. After his discharge from the second admission, his serum TSH levels fluctuated in accordance with serum FT3 and FT4 levels and symptoms, such as palpitations. Ten months after his discharge, he was admitted to our department again due to adrenal insufficiency and thyrotoxicosis with elevated serum TSH levels, suggesting cyclic SITSH. Although resistance to thyroid hormone (RTH) was not completely excluded, the pituitary tumor was removed by transsphenoidal surgery (TSS). A pathological diagnosis confirmed TSHoma. We herein report a case of TSHoma in which serum TSH, FT3, and FT4 levels fluctuated periodically. To the best of our knowledge, this is the first case report of “cyclic TSHoma”, which needs to be considered when making a differential diagnosis of SITSH.

  • Yan Cao, Xinyu Li, Chong Lu, Xiaorong Zhan
    原稿種別: Original
    2018 年 65 巻 7 号 p. 747-753
    発行日: 2018年
    公開日: 2018/07/28
    [早期公開] 公開日: 2018/05/18
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    The World Health Organization (WHO) estimates that approximately 300 million people will suffer from diabetes mellitus by 2025. Type 2 diabetes mellitus (T2DM) is much more prevalent. T2DM comprises approximately 90% of diabetes mellitus cases, and it is caused by a combination of insulin resistance and inadequate compensatory insulin secretory response. In this study, we aimed to compare the plasma vitronectin (VN) levels between patients with T2DM and insulin resistance (IR) and healthy controls. Seventy patients with IR and 70 age- and body mass index (BMI)-matched healthy controls were included in the study. The insulin, Waist-to-Hip Ratio (WHR), C-peptide (CP) and VN levels of all participants were examined. The homeostasis model of assessment for insulin resistence index (HOMA-IR (CP)) formula was used to calculate insulin resistance. The levels of BMI, fasting plasma gluose (FPG), 2-hour postprandial glucose (2hPG), glycated hemoglobins (HbA1c), and HOMA-IR (CP) were significantly elevated in case group compared with controls. VN was found to be significantly decreased in case group. (VN Mean (Std): 8.55 (2.92) versus 12.88 (1.26) ng/mL p < 0.001). Multiple linear regression analysis was performed. This model explained 43.42% of the total variability of VN. Multiple linear regression analysis showed that HOMA-IR (CP) and age independently predicted VN levels. The VN may be a candidate target for the appraisal of hepatic insulin resistance in patients with T2DM.

  • Minako Inoue, Ken Okamura, Chie Kitaoka, Fumio Kinoshita, Ryo Namitome ...
    原稿種別: Original
    2018 年 65 巻 7 号 p. 755-767
    発行日: 2018年
    公開日: 2018/07/28
    [早期公開] 公開日: 2018/05/15
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    In ectopic ACTH-secreting pheochromocytoma, combined ACTH-driven hypercortisolemia and hypercatecholaminemia are serious conditions, which can be fatal if not diagnosed and managed appropriately, especially when glucocorticoid-driven positive feedback is suggested with a high ACTH/cortisol ratio. A 46-year-old man presented with headache, rapid weight loss, hyperhidrosis, severe hypertension and hyperglycemia without typical Cushingoid appearance. Endocrinological examinations demonstrated elevated plasma and urine catecholamines, serum cortisol and plasma ACTH. Moreover, his ACTH/cortisol ratio and catecholamine levels were extremely high, suggesting catecholamine-dominant ACTH-secreting pheochromocytoma. Computed tomography revealed a large right adrenal tumor. 18F-FDG positron emission tomography showed uptake in the area of the adrenal tumor, while 123I-metaiodobenzylguanidine scintigraphy showed no accumulation. His plasma ACTH level paradoxically became elevated after a dexamethasone suppression test. After metyrapone administration, not only serum cortisol but also plasma ACTH levels were exponentially decreased almost in parallel, suggesting a glucocorticoid-driven positive-feedback regulation in this rapidly exacerbated ectopic ACTH-producing pheochromocytoma. Interestingly enough, plasma catecholamine levels were also decreased by metyrapone, although they remained extremely high. He became severely dehydrated due to hypoadrenalism requiring hydrocortisone supplementation. His clinical signs and symptoms were improved, and right adrenalectomy was performed uneventfully, resulting in complete remission of pheochromocytoma and Cushing’s syndrome. A glucocorticoid-driven positive-feedback regulation in this ectopic ACTH-secreting pheochromocytoma created a vicious cycle with rapid exacerbation of both hypercortisolemia and hypercatecholaminemia with extremely elevated plasma ACTH level. Metyrapone was clinically effective to stop this vicious cycle; nonetheless, great care must be taken to avoid hypoadrenalism especially when hypercatecholaminemia remained.

  • Maojun Liu, Zining Li, Biao Liang, Ling Li, Shengquan Liu, Wenting Tan ...
    原稿種別: Original
    2018 年 65 巻 7 号 p. 769-781
    発行日: 2018年
    公開日: 2018/07/28
    [早期公開] 公開日: 2018/05/09
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    This study aims to investigate the role and regulatory mechanism of the Hydrogen sulfide (H2S) in amelioration of rat myocardial fibrosis induced by thyroxine through interfering the autophagy via regulating the activity of PI3K/AKT1 signaling pathway and the expression of relative miRNA. 40 adult male SD rats were randomly divided into 4 groups (n = 10): the control group, the thyroxine model group (TH group), the model group with H2S intervention (TH + H2S group) and the normal group with H2S intervention (H2S group). Pathological changes were observed via H&E staining and Masson staining, Expressions of MMPs/TIMPs, PI3K/AKT, autophagy-related proteins in myocardial tissues were detected via Western blotting, and the expressions of miR-21, miR-34a, miR-214 and miR-221 were detected via RT-qPCR. Compared with the control group, in the TH group, myocardial fibrosis was more significant, the expressions of proteins in PI3K/AKT and autophagy-related proteins were significantly decreased, as well as the expression of miR-221; while the expressions of miR-21, miR-34a and miR-214 were significantly elevated. By contrast, all above-mentioned changes were obviously reversed with H2S treatment, which demonstrated the positive function of H2S in amelioration of rat myocardial fibrosis induced by thyroxine. The mechanism of such amelioration may be correlated with autophagy activated by the upregulation of expression of PI3K/AKT signaling pathway and downregulation of expressions of miR-21, miR-34a and miR-214.

NOTE
  • Boyu Chen, Zhiqiang Li, Jianhua Chen, Jue Ji, Jingyi Shen, Yufeng Xu, ...
    原稿種別: Note
    2018 年 65 巻 7 号 p. 783-791
    発行日: 2018年
    公開日: 2018/07/28
    [早期公開] 公開日: 2018/04/14
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    Body mass index (BMI) is the most commonly used quantitative measure of adiposity. It is a kind of complex genetic diseases which are caused by multiple susceptibility genes. The first intron of fat mass and obesity-associated (FTO) has been widely discovered to be associated with BMI. Retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L) is located in the upstream region of FTO and has been proved to be linked with obesity through functional tests. We carried out a genetic association analysis to figure out the role of the FTO gene and the RPGRIP1L gene in BMI. A quantitative traits study with 6,102 Chinese female samples, adjusted for age, was performed during our project. Among the twelve SNPs, rs1421085, rs1558902, rs17817449, rs8050136, rs9939609, rs7202296, rs56137030, rs9930506 and rs12149832 in the FTO gene were significantly associated with BMI after Bonferroni correction. Meanwhile, rs9934800 in the RPGRIP1L gene showed significance with BMI before Bonferroni correction, but this association was eliminated after Bonferroni correction. Our results suggested that genetic variants in the FTO gene were strongly associated with BMI in Chinese women, which may serve as targets of pharmaceutical research and development concerning BMI. Meanwhile, we didn’t found the significant association between RPGRIP1L and BMI in Chinese women.

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