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Takata H.,Metabolism and Nephrology
Nihon rinsho. Japanese journal of clinical medicine | Year: 2013

Metabolic syndrome (Mets) is a combination of disorders including abdominal obesity, impaired glucose tolerance, dyslipidemia and hypertension, which increases risk for cardiovascular disease (CVD) and type 2 diabetes when occurring together. In Japan, diagnosis criteria of Mets consists of an increased waist circumference and 2 or more of CVD risk factors. Annual health checkups and health guidance using Mets criteria were established in 2008 for the prevention of life-style related diseases in Japan. In this issue, history and diagnostic criteria of Mets and concerns for Mets concept were described. Source

Tsukamoto N.,Okayama University of Science | Otsuka F.,Okayama University of Science | Miyoshi T.,Okayama University of Science | Yamanaka R.,Okayama University of Science | And 8 more authors.
Endocrinology | Year: 2010

The mechanism by which somatostatin analogs suppress ACTH production by corticotropinomas has yet to be fully elucidated. We here studied the effects of somatostatin analogs on ACTH secretion using mouse corticotrope AtT20 cells focusing on the biological activity of bone morphogenetic proteins (BMPs). BMP ligands, receptors and Smads, and somatostatin receptors (SSTRs)-2, -3, and -5 were expressed in AtT20 cells. BMP-2, -4, -6, and -7 decreased basal ACTH production with BMP-4 effects being the most prominent. BMP-4 also inhibited CRH-inducedACTH production and proopiomelanocortin (POMC) transcription. However, the decrease in CRH-induced cAMP accumulation caused by BMP-4 was not sufficient to completely account for BMP-4 actions, indicating that ACTH suppression by BMPs was not directly linked to cAMP inhibition. CRH-activated ERK1/ERK2, p38-MAPK, stress-activated protein kinase/c-Jun NH2-terminal kinase, protein kinase C, and Akt pathways and CRH-induced ACTH synthesis was significantly decreased in the presence of U0126 or SB203580. Because BMPs attenuated CRH-induced ERK and p38 phosphorylation, it was suggested that BMP-4 suppresses ACTH production by inhibiting CRH-induced ERK and p38 phosphorylation. Somatostatin analogs octreotide and pasireotide (SOM230) significantly suppressed CRH-induced ACTH and cAMP production in AtT20 cells and reduced ERK and p38 phosphorylation. Notably, CRH-induced ACTH production was enhanced in the presence of noggin, a BMP-binding protein. The inhibitory effects of octreotide and SOM230 on CRH-induced ACTHproductionwerealso attenuated by noggin, implying that the endogenous BMP system plays a key role in inhibiting CRH-induced ACTH production by AtT20 cells. The findings that OCT and SOM230 up-regulated BMP-Smad1/Smad5/Smad8 signaling and ALK-3 and BMPRII and downregulated inhibitory Smad6/7 establish that the activation of endogenous BMP system is functionally involved in the mechanism by which somatostatin analogs suppress CRH-induced ACTH production. Copyright © 2010 by The Endocrine Society. Source

Otsuka F.,Okayama University of Science | Tsukamoto N.,Okayama University of Science | Miyoshi T.,Okayama University of Science | Iwasaki Y.,Metabolism and Nephrology | Makino H.,Okayama University of Science
Molecular and Cellular Endocrinology | Year: 2012

The existence of a functional bone morphogenetic protein (BMP) system in the pituitary has been recognized. Recent studies have provided evidence that BMPs elicit differential actions in the regulation of prolactin (PRL) and adrenocorticotropin (ACTH) release in lactotropinoma and corticotropinoma cells, respectively. BMPs play a key role in the modulation of somatostatin receptor (SSTR) sensitivity of lactosomatotrope cells in an autocrine/paracrine manner. In addition, SSTR action enhances BMP responsiveness in corticotrope cells. The functional link between BMP receptor signaling and SSTR actions may be crucial for individual tolerance to somatostatin analogs for controlling PRL and ACTH production. Adjustment of the endogenous SSTR sensitivity may be an effective strategy to inhibit the growth activity and hormonal productivity of intractable pituitary tumors. © 2011 Elsevier Ireland Ltd. Source

Makino S.,Osaka Gyomeikan Hospital | Fujiwara M.,Osaka Gyomeikan Hospital | Handa H.,Osaka Gyomeikan Hospital | Fujie T.,Osaka Gyomeikan Hospital | And 4 more authors.
Clinical Endocrinology | Year: 2012

Context: We aimed to assess whether obstructive sleep apnoea syndrome (OSAS) affects plasma IGF-1 and dehydroepiandrosterone sulphate (DHEA-S) levels in men, factors implicated in the development of age-related metabolic disorders. Design: We conducted a cross-sectional and longitudinal clinical study. Patients and setting: We measured plasma IGF-1 and DHEA-S levels in 191 non-drug-treated Japanese men (34 primary snorers (PS), 88 patients with mild-to-moderate OSAS and 69 patients severe OSAS ). Results: Plasma IGF-1 and DHEA-S were negatively correlated with age. Plasma IGF-1 was also negatively correlated with plasma glucose, HOMA-IR and systolic blood pressure and apnoea parameters such as the apnoea-hypopnea index, minimum oxygen saturation and slow-wave sleep (SWS) time. Plasma DHEA-S was associated with plasma glucose, HbA1c and free fatty acid and was negatively correlated with SWS time. To eliminate the influence of age, PS, patients with mild-to-moderate OSAS and severe OSAS were divided into three groups by age: young (<40 years), middleaged (40-59 years) and elderly (≥60 years). Patients with severe OSAS aged <40 or <60 years had lower plasma IGF-1 or DHEA-S levels, respectively, than did the corresponding snorers and mildto- moderate OSAS groups. Continuous positive airway pressure therapy for generally 16-18 months increased plasma IGF-1 levels in patients with severe OSAS aged <40 years (n = 18). Plasma DHEA-S levels were increased in patients with severe OSAS aged <60 years, whose DHEA-S level was below the mean value for that age (n = 23/41). Conclusion: Severe OSAS could reduce plasma IGF-1 and DHEAS levels in younger, but not elderly Japanese men, which is potentially associated with the development of metabolic abnormalities. © 2012 Blackwell Publishing Ltd. Source

Horino T.,Metabolism and Nephrology | Takao T.,Kochi Medical School | Taniguchi Y.,Metabolism and Nephrology | Terada Y.,Metabolism and Nephrology
Clinical Rheumatology | Year: 2010

A 75-year-old man presented with headache, right facial palsy, and left hemiparesis. Because of elevated myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titers and findings from magnetic resonance imaging (MRI) which were compatible with hypertrophic pachymeningitis (HP), he was diagnosed with MPO-ANCA-positive HP. He was treated with the combination therapy of steroid and cyclophosphamide (CY), leading to good prognosis. We present a case of HP associated with MPO-ANCA-positive vasculitis and emphasize the importance of MPO-ANCA tests as a predictable factor for relapse of the disease in order to start earlier treatment for the disease. © 2009 Clinical Rheumatology. Source

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