Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959
Volume 55 , Issue 4
Showing 1-22 articles out of 22 articles from the selected issue
REVIEWS
  • Katsumi IIZUKA, Yukio HORIKAWA
    2008 Volume 55 Issue 4 Pages 617-624
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 19, 2008
    JOURNALS FREE ACCESS
    Excess carbohydrate intake leads to fat accumulation and insulin resistance. Glucose and insulin coordinately regulate de novo lipogenesis from glucose in the liver, and insulin activates several transcription factors including SREBP1c and LXR, while those activated by glucose remain unknown. Recently, a carbohydrate response element binding protein (ChREBP), which binds to the carbohydrate response element (ChoRE) in the promoter of rat liver type pyruvate kinase (LPK), has been identified. The target genes of ChREBP are involved in glycolysis, lipogenesis, and gluconeogenesis. Although the regulation of ChREBP remains unknown in detail, the transactivity of ChREBP is partly regulated by a phosphorylation/dephosphorylation mechanism. During fasting, protein kinase A and AMP-activated protein kinase phosphorylate ChREBP and inactivate its transactivity. During feeding, xylulose-5-phosphate in the hexose monophosphate pathway activates protein phosphatase 2A, which dephosphorylates ChREBP and activates its transactivity. ChREBP controls 50% of hepatic lipogenesis by regulating glycolytic and lipogenic gene expression. In ChREBP -/- mice, liver triglyceride content is decreased and liver glycogen content is increased compared to wild-type mice. These results indicate that ChREBP can regulate metabolic gene expression to convert excess carbohydrate into triglyceride rather than glycogen. Furthermore, complete inhibition of ChREBP in ob/ob mice reduces the effects of the metabolic syndrome such as obesity, fatty liver, and glucose intolerance. Thus, further clarification of the physiological role of ChREBP may be useful in developing treatments for the metabolic syndrome.
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  • Alexandra OZIMEK, Joachim DIEBOLD, Rainer LINKE, Jens HEYN, Klaus HALL ...
    2008 Volume 55 Issue 4 Pages 625-638
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 19, 2008
    JOURNALS FREE ACCESS
    Most of the adrenal tumors that are incidentally detected are benign adenomas. The incidence of malignant adrenal tumors including adrenocortical carcinoma (ACC) and primary adrenal lymphoma (PAL) is rather low. As many patients with ACC and PAL are diagnosed at an advanced stage of disease, the overall survival time of both entities remains poor. The therapeutic strategies for both entities differ. Thus an early differentiation between ACC and PAL is necessary. Unfortunately hitherto preoperative diagnosis of potentially malignant adrenal masses is still a main problem in the treatment of adrenal tumors. We present the case of a 57-year-old male patient with ACC and the case of an 87-year-old male patient with PAL and provide a systematic comparison of the clinical and pathological features of both entities. In both cases clinical and radiological features resulted in an initially false diagnosis. Primary surgical therapy was performed in both patients. The patient with PAL died five months aftre initial surgery. The patient with ACC showed tumor progression with local and systemic recurrence despite adjuvant therapy with mitotane and additional surgical therapy. Prognosis of patients with ACC and PAL seems to be dependant on the ability to start accurate treatment without any time delay. We propose some guidelines for diagnosis and surgical management of adrenal tumors.
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ORIGINALS
  • Luís M. ROSÁRIO, Rui M. BARBOSA, Célia M. ANTUNES ...
    2008 Volume 55 Issue 4 Pages 639-650
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 21, 2008
    JOURNALS FREE ACCESS
    The glucose sensitivity of bursting electrical activity and pulsatile insulin release from pancreatic islets was determined in absence of functional KATP channels. Membrane potential, [Ca2+]i and 5-HT/insulin release were measured by intracellular recording, fura-2 fluorescence and 5-HT amperometry, respectively. Single mouse islets, bathed in tolbutamide or glibenclamide and high extracellular Ca2+ (Ca2+o), displayed bursting activity and concomitant fast [Ca2+]i and 5-HT/insulin oscillations. Sulphonylurea block of KATP channel current was unaffected by raising Ca2+o. Raising glucose or α-ketoisocaproic acid (KIC) concentration from 3 to 30 mM increased spiking activity and burst plateau duration. Staurosporine did not impair glucose potentiation of electrical activity, ruling out the involvement of serine/threonine kinases. Glucose enhanced both [Ca2+]i and 5-HT/insulin oscillatory activity, causing a ~3-fold increase in overall 5-HT release rate. Cells lacking bursting activity in high Ca2+o and low glucose (or KIC) developed a pattern of intensified spiking in response to 11 mM glucose. It is concluded that β-cells exhibit graded oscillatory electrical and secretory responses to glucose in absence of functional KATP channels. This suggests that, under physiological conditions, early glucose sensing may involve other channels besides the KATP channel.
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  • Tomoko HAYASHI, Miho MURATA, Tomoyuki SAITO, Aki IKOMA, Hiroyuki TAMEM ...
    2008 Volume 55 Issue 4 Pages 651-655
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 21, 2008
    JOURNALS FREE ACCESS
    The present study was undertaken to determine pathophysiology of body water control in hypernatremic subjects with hypothalamic space-occupying lesions. Eight subjects with hypothalamic space-occupying lesions were divided into two groups of hypernatremia in the presence or absence of body water deficit. In 5 dehydrated hypernatremic subjects whose ages ranged from 20 to 67 years, serum sodium (Na) levels were 156.4 ± 3.1 mmol/l; plasma osmolality (Posm), 320.6 ± 9.8 mmol/kg; and urinary osmolality (Uosm), 246.8 ± 46.7 mmol/kg under ad libitum water drinking. In 3 non-dehydrated hypernatremic subjects whose ages ranged from 21 to 32 years, serum Na levels were 150.3 ± 5.4 mmol/l; Posm, 300.3 ± 11.6 mmol/kg; and Uosm, 738.7 ± 237.1 mmol/kg. Serum Na levels had a positive correlation with hematocrit (Ht) in 2 of 5 subjects with dehydration, but it totally disappeared in the 3 subjects without dehydration. Plasma arginine vasopressin (AVP) levels were 0.7 ± 0.1 pmol/l, and there was no response of AVP release to intravenous administration of 5% NaCl in the subjects with dehydration. Plasma AVP was 0.7 ± 0.1 pmol/l, and there was the reduced response of AVP release to 5% NaCl in those without dehydration. In one of 3 subjects a positive correlation between Posm and plasma AVP levels was obtained. Drinking behavior was totally abolished in the subjects with dehydration, and partly reduced in those without dehydration. The present study indicates that hypothalamic space-occupying lesions causes central diabetes insipidus and hypodipsia, and that sporadic and paradoxical release of AVP, enhanced renal concentrating ability and reduced drinking behavior may possess body water minimally in the hypernatremic subjects without water deficit.
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  • Takeshi HOSOYA, Tsuyoshi MONDEN, Yoshitatsu FUKABORI, Koshi HASHIMOTO, ...
    2008 Volume 55 Issue 4 Pages 657-665
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: June 18, 2008
    JOURNALS FREE ACCESS
    We cloned a novel splicing variant for nuclear coactivator p120(α), designated as p120β and studied its function and expression in several human prostate diseases. Transfection assays demonstrated that p120β functions as a strong coactivator for androgen receptor (AR), but weakly for other nuclear receptors. GST-pull down assay showed that a glutamine-rich region of the p120 bound to the ligand-binding domain of AR. Interestingly, p120β mRNAs were expressed predominantly in the normal prostate, androgen-responsive prostate cancers and an androgen-sensitive prostate cancer cell line, LNCaP, but weakly in recurrent cancers and the androgen-insensitive prostate cancer cell lines PC3 and DU145. Furthermore, knockdown of p120α by siRNA abolished coactivator activity on thyroid hormone receptors (TR) and PPARγ, but did not affect that of ARs in PC3 cells. In addition, competitive assay with other nuclear receptors demonstrated that TR and PPARγ did not inhibit p120β-induced stimulation. These findings suggested that while p120α was essential for ligand-dependent stimulation of TRs and PPARγ, p120β acted as a coactivating protein predominantly for AR.
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  • Ippei KANAZAWA, Toru YAMAGUCHI, Masahiro YAMAMOTO, Mika YAMAUCHI, Soic ...
    2008 Volume 55 Issue 4 Pages 667-675
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 21, 2008
    JOURNALS FREE ACCESS
    We investigated the relationship between serum dehydroepiandrosterone-sulfate (DHEA-S) and insulin-like growth factor-I (IGF-I) to various parameters for atherosclerosis in type 2 diabetes. The levels of DHEA-S and IGF-I are known to decrease with aging and thereby might be associated with an increased risk of cardiovascular disease. One hundred forty-eight men and 106 postmenopausal women with type 2 diabetes were assessed in a cross-sectional study. Serum DHEA-S and IGF-I concentrations were measured and brachial-ankle pulse wave velocity (baPWV) and ultrasonographically-evaluated intima-media thickness (IMT) were assessed. Although simple regression analysis showed that log(DHEA-S) and IGF-I in men and log(DHEA-S) in women were significantly and inversely correlated with baPWV and IMT, only log(DHEA-S) in women was still significantly and inversely correlated with these atherosclerotic parameters after multiple regression analysis was adjusted for age, duration of diabetes, BMI, HbA1C, systolic blood pressure, LDL-Cholesterol (C), serum creatinine, and smoking (Brinkman index). Serum DHEA-S level seemed to be associated with atherosclerosis in diabetic postmenopausal women independent of age, body stature, diabetic status, and other atherosclerotic risk factors, and might be a useful addition to other parameters for assessing the risk of atherosclerosis in this population.
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  • Ken KATO, Munehide MATSUHISA, Naotsugu ICHIMARU, Shiro TAKAHARA, Yasuy ...
    2008 Volume 55 Issue 4 Pages 677-683
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: June 18, 2008
    JOURNALS FREE ACCESS
    New-onset diabetes after renal transplantation (NODAT) is known to be a potent risk factor for cardiovascular events. We therefore investigated the incidence and risk factors for NODAT, and evaluated surrogate endpoints of atherosclerosis in Japanese patients with stable renal function after renal transplantation. Seventy-nine patients were enrolled in the study, and a 75 g oral glucose tolerance test (OGTT) was performed in subjects excluding patients with known NODAT. We evaluated the risk factors for NODAT and the degree of atherosclerosis, determined by brachial-ankle pulse wave velocity (baPWV), ankle-brachial blood pressure index (ABPI) and intima-media thickness (IMT) of the carotid artery. Eleven patients diagnosed as NODAT had significantly higher fasting plasma glucose before transplantation, blood pressure, and incidence of hepatitis C virus (HCV) infection than patients without NODAT. Multivariate regression analysis revealed that the independent determinant of NODAT was fasting plasma glucose pre-transplantation, HCV infection and systolic blood pressure. The baPWV in patients with NODAT was significantly higher compared to that in patients without NODAT. In addition, the independent determinant of baPWV evaluated by multivariate regression analysis was an increase in systolic blood pressure and age, and a decrease of adiponectin levels. In conclusion, we found that high fasting plasma glucose prior to transplantation, HCV infection and high blood pressure are risk factors for NODAT in Japanese patients after renal transplantation. Since NODAT patients have advanced arterial stiffness probably due to high blood pressure, strict control of blood pressure will be important for preventing the development of cardiovascular disease in NODAT.
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  • Carlo CAPPELLI, Andrea TIRONI, Gian Pietro MARCHETTI, Ilenia PIROLA, E ...
    2008 Volume 55 Issue 4 Pages 685-690
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: June 18, 2008
    JOURNALS FREE ACCESS
    Carcinoma showing thymic-like differentiation (CASTLE) is a rare tumour of the thyroid, which arises from ectopic thymic tissue or remnants of branchial pouches. A systematic review of English literature evidences less than thirty cases; from them, it clearly appears that CASTLE is considered an indolent slow-growing neoplasia even when lymph nodes metastasis are present. We describe a case of very aggressive CASTLE, which showed seeding along fine needle aspiration tract.
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  • Takeshi OGIHARA, Yoshio FUJITANI, Toyoyoshi UCHIDA, Rei KANNO, Jong Bo ...
    2008 Volume 55 Issue 4 Pages 691-698
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 28, 2008
    JOURNALS FREE ACCESS
    Neurogenin 3 (Ngn3) is a transcription factor that regulates an initial step of differentiation from uncommitted pancreatic progenitors into endocrine cells. Additional transcription factors are required for complete differentiation into mature pancreatic beta cells. In this study, we established an in vitro model system of beta-cell differentiation by adenovirus-mediated expression of several transcription factors in AR42J-B13 cells, a pancreatic progenitor-like cell line derived from exocrine pancreas. Exogenous expression of Ngn3 in AR42J-B13 cells induced expression of Nkx2.2, Pax4, and Pax6, which are all essential for beta-cell differentiation in mouse embryos. However, Ngn3 did not induce more downstream regulators of beta-cell differentiation, Nkx6.1 and Maf A. Coexpression of Nkx6.1 and Ngn3 induced endogenous expression of the insulin 2 gene, while coexpression of Maf A and Ngn3 induced both insulin 1 and 2 genes in AR42J-B13 cells. Our data demonstrated that Ngn3 expressed together with Nkx6.1 or MafA induces AR42J-B13 cells to differentiate into insulin-producing cells, supporting the use of these cells as a model system for studying beta-cell differentiation in vitro.
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  • Masako ZENIBAYASHI, Kazuaki MIYAKE, Yukio HORIKAWA, Yushi HIROTA, Tets ...
    2008 Volume 55 Issue 4 Pages 699-707
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 21, 2008
    JOURNALS FREE ACCESS
    Aims. A missense mutation in the low density lipoprotein receptor-related protein 6 gene (LRP6) was recently shown to be responsible for a disorder characterized by early-onset coronary artery disease as well as diabetes mellitus (DM), hyperlipidemia, hypertension, and osteoporosis. Mice deficient in LRP5, a closely related paralog of LRP6, manifest a marked impairment in glucose tolerance. The aim of the present study was to examine whether common variants of LRP5 and LRP6 are associated with Type 2 DM or dyslipidemia in Japanese individuals. Methods. Thirteen single nucleotide polymorphisms (SNPs) of LRP6 and nine SNPs of LRP5 were genotyped in a total of 608 Type 2 DM patients and 366 nondiabetic control subjects (initial study). An association analysis was then performed for each SNP and for haplotypes. For some of the SNPs, we provided another sample panel of 576 cases and 576 controls for the replication study. The relation to clinical characteristics was also examined in diabetic subjects. Results. In the initial study, three SNPs of LRP6 were found to be associated with susceptibility to Type 2 DM. However, this association was not detected in the replication panel. None of SNPs in LRP5 were associated with Type 2 DM in the initial panel. Neither LRP6 nor LRP5 was associated with body mass index, HOMA-β, HOMA-IR or serum lipid concentrations. Conclusions. We found no evidence for a substantial effect of LRP5 or LRP6 SNPs on susceptibility to type 2 diabetes or clinical characteristics of diabetic subjects in Japanese population.
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  • Hiroshi ARAI, Nozomi KOBAYASHI, Yuko NAKATSURU, Hiroaki MASUZAKI, Taku ...
    2008 Volume 55 Issue 4 Pages 709-715
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 21, 2008
    JOURNALS FREE ACCESS
    This report concerns a case of cortisol-producing adrenocortical adenoma without the phenotype of Cushing's syndrome. A left adrenal tumor was incidentally detected in this patient. A diagnosis of adrenal Cushing's syndrome was based on the results of endocrinological and radiological examinations, although she showed none of the physical signs of Cushing's syndrome, glucose intolerance, hypertension or dyslipidermia. After a successful laparoscopic left adrenalectomy, the pathological diagnosis was adrenocortical adenoma. Slow tapering of glucocorticoids was needed to prevent adrenal insufficiency after surgery, and the plasma ACTH level remained high even though the serum cortisol level had reached the upper limit of the normal range. Further examination showed a urinary THF + allo-THF/THE ratio of 0.63, which was lower than that of control (0.90 ± 0.13, mean ± SD). Serum cortisol/cortisone ratios after the cortisone acetate administration were also decreased, and the serum half-life of cortisol was shorter than the normal range which has been reported. These findings indicated a partial defect in 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity, which converts cortisone to cortisol. Our case suggests that a change in 11β-HSD1 activity results in inter-individual differences in glucocorticoid efficacy.
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  • Iraj NABIPOUR, Katayoun VAHDAT, Seyed Mojtaba JAFARI, Saeideh BEIGI, M ...
    2008 Volume 55 Issue 4 Pages 717-722
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 21, 2008
    JOURNALS FREE ACCESS
    Previous studies have suggested that low-grade systemic inflammation is involved in the pathogenesis of type 2 diabetes mellitus. However, limited information is available about the relationship of diabetes mellitus and inflammation in Asia. We examined the association between high-sensitivity C-reactive protein (CRP) levels and diabetes in a general Iranian population. In an ancillary study to the Persian Gulf Healthy Heart Study, a cohort study of men and women aged ≥25 years, a random sample of 1754 (49.2 percent males, 50.8 percent females) subjects were evaluated. High sensitivity C-reactive protein was measured by enzyme-linked immunosorbent assay. Elevated serum CRP was defined as more than 3.0 mg/l. The diabetes classification was based on the criteria of the American Diabetes Association. A total of 8.6 percent of the subjects (8.0 percent of males & 9.1 percent of females; p>0.05) had type 2 diabetes mellitus. Geometric mean of CRP was 1.94 mg/l (3.80 SD) in the studied population. The subjects with diabetes had a higher geometric mean of CRP levels than the subjects with no diabetes [3.67 (SD 3.71) versus 1.85 (3.83) respectively; p<0.0001)]. In multiple logistic regression analysis, diabetes showed a significant age-adjusted association with elevated CRP levels [Odds Ratio = 2.03, Confidence Interval (1.38-2.98); p<0.0001] after adjusting for sex, LDL-cholesterol, HDL-cholesterol blood pressure, smoking and body mass index. In conclusion, beyond traditional cardiovascular risk factors, elevated CRP is significantly correlated with diabetes in general population of the northern Persian Gulf. Further insight into the specific effects of proinflammatory cytokines and acute-phase proteins will be essential for the development of new preventive strategies for diabetes mellitus.
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  • Yoshihiro ISAKA, Katsunobu YOSHIOKA, Minako NISHIO, Keiko YAMAGAMI, Yo ...
    2008 Volume 55 Issue 4 Pages 723-728
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 21, 2008
    JOURNALS FREE ACCESS
    A 55-years-old man was admitted to our hospital with a 6-month history of general fatigue, purulent nasal discharge, polyuria, and polydipsia. Endocrinological findings revealed central diabetes insipidus (CDI) with mild anterior pituitary dysfunction. Imaging studies revealed thickening of the proximal end of the pituitary stalk just below the third ventricle, a mass in the paranasal sinus, and a mass encompassing the abdominal aorta. Histopathology of the mass in the paranasal sinus revealed abundant IgG4-positive plasma cells, and the IgG4 serum level was markedly elevated. Thus, he was diagnosed with IgG4-related multifocal fibrosclerosis. Therapy with prednisolone resulted in complete resolution of clinical symptoms and reduction in size of the masses in the affected organs. However, CDI remained unchanged. This is the first case in which the cause of CDI was IgG4-related multifocal fibrosclerosis. IgG4-related sclerosing disease should be included in the differential diagnosis of thickening of the pituitary stalk with CDI, and a search for extra-pituitary involvement is essential.
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  • Daniel J. CUTHBERTSON, Dave RITCHIE, Daniel CROOKS, Gavin MAIN, Colin ...
    2008 Volume 55 Issue 4 Pages 729-735
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 23, 2008
    JOURNALS FREE ACCESS
    Lymphocytic Hypophysitis (LH) is a rare and previously under-recognised disorder, most commonly affecting young females in the post-partum period. It presents clinically with symptoms and signs related to either a pituitary mass or hypopituitarism, frequently mimicking a pituitary adenoma; the diagnosis of LH can only be made histologically with the presence of a dense lymphocytic infiltration usually confined to the anterior pituitary. We present two case histories of patients who presented with symptoms suggestive of a functioning pituitary adenoma who also had concomitant LH confirmed histologically. The first case was a 39 year old lady, with a history of primary hypothyroidism, who presented with weight gain and hirsutism and clinical and biochemical features of Cushing's syndrome. The second case was a 61 year old male, also with a history of primary hypothyroidism, who presented with visual field loss and biochemically with hyperprolactinaemia. In both patients, magnetic resonance (MR) imaging of the pituitary demonstrated an enlarged partially cystic pituitary mass with slight suprasellar extension. Both patients were treated surgically with transphenoidal drainage and excision and histological examination of the surgical specimens demonstrated a mixture of pathologies with fragments of adenohypophyseal tissue (staining positive for ACTH and prolactin respectively) with a dense chronic inflammatory cell infiltrate suggestive of LH in nearby normal anterior pituitary. In both cases a joint diagnosis of a functioning pituitary adenoma with LH was made. There have been only several reported cases of this combination of pathologies but LH even in isolation is becoming increasingly recognised.
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  • Mika TSUIKI, Akiyo TANABE, Sachiko TAKAGI, Mitsuhide NARUSE, Kazue TAK ...
    2008 Volume 55 Issue 4 Pages 737-745
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 28, 2008
    JOURNALS FREE ACCESS
    Although subclinical Cushing's syndrome has been commonly experienced, details of the clinical outcome and its indication for adrenalectomy have yet to be established. In the present study, we investigated the prevalence of cardiovascular risks, their clinical outcome during long-term follow up before and after adrenalectomy in 20 patients with subclinical Cushing's syndrome. We also correlated the hypercortisolism and age with the cardiovascular risks and the clinical outcome. The prevalence of hypertension, impaired glucose metabolism, dyslipidemia, and obesity was 45%, 65%, 65%, and 25%, respectively. In the non-operated group (n = 12), six patients (50%) showed deterioration of at least one of the cardiovascular risks. Four patients showed an increase of at least one risk, while none of the patients showed a decrease in the number of risks. One patient developed overt Cushing's syndrome. In the operated group (n = 10) including two operated patients of the non-operated group, eight patients (80%) showed an improvement of at least one of the cardiovascular risks after surgery and five patients (50%) showed a decrease of at least one risk. The prognosis in terms of the changes of the cardiovascular risks was significantly better in the operated group than in the non-operated group (p<0.001). Neither the hypercortisolism nor age correlated to the presence and the clinical outcome of the cardiovascular risks. The present study clearly demonstrated probability of deterioration during the clinical course and improvement after adrenal surgery in patients with subclinical Cushing's syndrome. Careful follow-up of the cardiovascular risks is therefore warranted. Adrenalectomy could be a treatment of choice despite the hypercortisolism and age of the patients, especially when the cardiovascular risks show signs of deterioration.
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  • Xiu-ping BI, Hong-wei TAN, Shan-shan XING, Zhi-hao WANG, Meng-xiong TA ...
    2008 Volume 55 Issue 4 Pages 747-752
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 23, 2008
    JOURNALS FREE ACCESS
    Insulin resistance is the physiopathologic foundation of metabolic syndrome. TRB3 has been revealed to be involved in insulin resistance in the liver by interacting directly with Akt and blocking its activation. Our investigation aims at exploring the relationship between metabolic syndrome and TRB3 mRNA expression in adipose tissue of rats. Two groups were studied as follows: the control group (Control, n = 12) was fed a standard rodent chow, and the experimental group (Fructose n = 9) was fed a high-fructose diet. Body weight and systolic blood pressure were measured per 4 weeks. At the end of 38 weeks, levels of tribbles mRNAs in adipose tissue were determined by quantitative real-time polymerase chain reaction (PCR), and Akt/phospho-Akt expression was assessed by Western blot. Results show that levels of TRB1-3 mRNAs were expressed in adipose tissue of rats of both groups, and tribbles mRNAs were TRB1 (Control: 0.00515, Fructose: 0.00497), TRB2 (Control: 0.02104, Fructose: 0.01988), and TRB3 (Control: 0.00457, Fructose: 0.00822), respectively. Of the three, TRB3 mRNA alone significantly increased by 94% in adipose tissue of fructose-fed rats compared with those in adipose tissue of the controls (P<0.05), and there was significant positive correlation between TRB3 mRNA levels and HOMA-R in fructose group (r = 0.68, P<0.05). Western blot analysis showed that phospho-Akt (Ser-473) expression was significantly decreased in adipose tissue of fructose-fed rats compared with controls (P<0.001). The present study suggests that TRB3 may be involved in metabolic syndrome by inhibiting activation of Akt in adipose tissue.
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NOTES
  • Hiroyuki SHIMIZU, Yutaka UEHARA, Shuichi OKADA, Masatomo MORI
    2008 Volume 55 Issue 4 Pages 753-756
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 23, 2008
    JOURNALS FREE ACCESS
    The contribution of fasting and postprandial glucose to hemoglobin A1c (HbA1c) levels was evaluated in insulin-treated patients. In 57 insulin-treated, diabetic out-patients, fasting glucose (before breakfast (B-FG), lunch (L-FG) and dinner (D-FG)) and postprandial glucose (B-PPG, L-PPG and D-PPG) levels were determined by the patients themselves at home using glucose self-monitoring apparatus over the course of one week. The correlation between HbA1c levels and self monitored blood glucose levels were calculated. In the conventionally treated group, there was a significant correlation between HbA1c and fasting glucose (FG) levels only before lunch, but at 2 hr after (PPG) all meals. In the intensively treated group, a significant correlation between HbA1c levels and FG levels was found before lunch and at 2 hr after breakfast and dinner. In all subjects, only FG levels before lunch correlated significantly with HbA1c levels, although PPG levels were significantly correlated with HbA1c at all points. The correlation was highest with PPG after breakfast and dinner. The sum of all FG, PPG and FG + PPG levels was significantly correlated with HbA1c levels. Postprandial hyperglycemia after breakfast and dinner should be regarded as most important for improving HbA1c levels in insulin treated diabetic patients.
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  • Yukako YOSHIKUMI, Hideki OHNO, Junko SUZUKI, Masashi ISSHIKI, Yasuyuki ...
    2008 Volume 55 Issue 4 Pages 757-765
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 28, 2008
    JOURNALS FREE ACCESS
    Pancreatic AR42J cells demonstrate the pluripotency in precursor cells of the gut endoderm and also provide an excellent model system to study the differentiation of the pancreas. Using the mRNA differential display technique, we identified junctional adhesion molecule-1 (JAM-1), a component of the tight junction, was highly up-regulated during the differentiation of AR42J cells, although junctions were not formed. The expression level of JAM-1 showed an up-regulation in the mRNA level after 3 hours and in the protein level after 24 hours in [activin A + betacellulin]-treated AR42J cells. The expressions of its signaling molecules, PAR-3 and atypical PKCλ, also increased after the addition of activin A + betacellulin. When JAM-1 was over-expressed in [activin A + betacellulin]-treated AR42J cells, tagged-JAM-1 was observed in cytoplasm as vesicular structures and JAM-1 was colocalized with Rab3B and Rab13, members of the Rab family expressed at tight junctions. In streptozotocin-induced regenerating islets, the expression of JAM-1 was also up-regulated in the mRNA level and the protein level. JAM-1 might therefore play an important role in the differentiation of AR42J cells and the regeneration of pancreatic islets.
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  • Katsuko TAKASAWA, Naoto KUBOTA, Yasuo TERAUCHI, Takashi KADOWAKI
    2008 Volume 55 Issue 4 Pages 767-776
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 28, 2008
    JOURNALS FREE ACCESS
    Peroxisome proliferator-activated receptor (PPAR)γ, a transcription factor belonging to the nuclear receptor superfamily, is essential for adipogenesis. PPARγ is recognized as a major target for the insulin-sensitizing effects of the thiazolidinediones. Previous studies have demonstrated that heterozygous PPARγ-deficient mice are protected from high-fat diet (HFD)-induced adipocyte hypertrophy, obesity and insulin resistance, which suggests that PPARγ may have a pivotal role in adipocyte hypertrophy, obesity and insulin resistance. In this study, we generated transgenic mice with the gain-of-function PPARγ Ser112Ala mutation (S112A mice) using the aP2 promoter, to elucidate the impact of increased PPARγ activity in mature adipocytes. Despite a 2-3-fold increase in the adipocyte PPARγ2 gene expression and PPARγ activity, the S112A mice showed comparable adiposity and insulin sensitivity to wild-type mice under both normal and HFD conditions. Although the expression levels of the PPARγ target genes involved in lipid metabolism, such as aP2 and stearoyl-CoA desaturase 1, were upregulated in the white adipose tissue of the S112A mice, the serum levels of free fatty acid, triglyceride, adiponectin and leptin, as well as the oxygen consumption, were comparable between the wild-type and S112A mice under the HFD condition. Moreover, treatment with rosiglitazone ameliorated insulin resistance and glucose intolerance to a similar degree in the two genotypes under the HFD condition. In conclusion, whereas the 50% decrease in PPAR γ activity showed protection from HFD-induced obesity and insulin resistance, in the present study, the 2-3-fold increase in PPARγ2 expression and PPARγ activity failed to show obesity and insulin resistance even under the HFD condition.
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  • Kazunori KAGEYAMA, Takeshi NIGAWARA, Satoru SAKIHARA, Shinobu TAKAYASU ...
    2008 Volume 55 Issue 4 Pages 777-783
    Published: 2008
    Released: August 27, 2008
    [Advance publication] Released: May 21, 2008
    JOURNALS FREE ACCESS
    Adrenal insufficiency can result from primary disorder of the adrenal gland or occurs secondarily due to deficiency in adrenocorticotropic hormone (ACTH) or corticotropin-releasing hormone (CRH). To prevent adrenal crisis, it is thus important to test the remaining function of the adrenal gland. Tests for the function of the hypothalamic-pituitary-adrenal (HPA) axis are also useful for examining localization of disease causing adrenal insufficiency. Generally, the insulin tolerance test (ITT) is useful for examining the HPA axis in both hypothalamic and pituitary diseases; however, ITT has a number of disadvantages. The growth hormone-releasing peptide (GHRP)-2 test may be a useful tool for diagnosing secondary adrenal insufficiency such as hypothalamic disorder and pituitary damage. In the present study, we examined the diagnostic usefulness of the GHRP-2 test as a substitute for ITT in hypopituitarism. We showed that patients with significant ACTH response to ITT also had significant response to the GHRP-2 test, while patients with no significant ACTH response to ITT also had no significant response to the GHRP-2 test. These data suggest that the GHRP-2 test may be a useful diagnostic tool for secondary adrenal insufficiency such as hypothalamic disorder and pituitary damage.
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