| 581. |
- Ottosson, Malin, 1959, et al.
(författare)
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The effects of cortisol on the regulation of lipoprotein lipase activity in human adipose tissue.
- 1994
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 79:3, s. 820-5
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Tidskriftsartikel (refereegranskat)abstract
- The influence of cortisol, in the presence of insulin, on the regulation of lipoprotein lipase (LPL) activity was studied in human adipose tissue, using a tissue incubation technique. Tissue pieces were preincubated for 3 days in a control medium containing insulin (7175 pmol/L), then incubated for 2 additional days in the control medium with and without cortisol (1000 nmol/L). After the 5 days of incubation, the levels of LPL messenger ribonucleic acid (mRNA), relative LPL synthesis, and LPL activity (total and heparin releasable) were studied. Cortisol exposure for 2 days increased all of the variables related to LPL. The average increase was 2.5-fold for LPL mRNA, 3.0-fold for relative LPL synthesis, 5.2-fold for total LPL activity, and 9.4-fold for heparin-releasable LPL activity compared to that in controls without cortisol. The results confirm previous findings that cortisol, in the presence of insulin, has a marked stimulatory effect on LPL activity in human adipose tissue in vitro. New data have been presented on the mechanisms of cortisol regulation of LPL activity. They involve both an increased level of LPL mRNA, leading to increased relative LPL synthesis, and additional posttranslational regulation.
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| 582. |
- Oystese, Kristin Astrid, et al.
(författare)
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Estrogen Receptor alpha, a Sex-Dependent Predictor of Aggressiveness in Nonfunctioning Pituitary Adenomas : SSTR and Sex Hormone Receptor Distribution in NFPA
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:9, s. 3581-3590
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Tidskriftsartikel (refereegranskat)abstract
- Context: Nonfunctioning pituitary adenomas (NFPAs) are fairly common and require a multidisciplinary approach. Reliable markers of a clinically aggressive course are lacking. Medical treatment is not available, and transsphenoidal surgery is the preferred primary treatment. Objective: We aimed to characterize the somatostatin, estrogen, and progesterone receptor distribution for NFPAs and compare it with factors of tumor aggressiveness. Design: Tumor samples for immunohistochemistry (n = 145) and quantitative reverse transcription polymerase chain reaction (n = 106) analyses of somatostatin receptor (SSTR) 1, SSTR2, SSTR3, SSTR5, estrogen receptor alpha (ER alpha), and progesterone receptor (PR) were measured by immunoreactive score (IRS) andmessenger RNA relative quantity and retrospectively compared with variables of aggressiveness. Setting: All patients were operated at the same tertiary referral center. Participants: A total of 164 patients with NFPA and tumor tissue from the primary operation were included. Results: SSTR3 was expressed abundantly by immunohistochemistry in all NFPAs. The IRS of ER alpha correlated with that of SSTR2 in male patients only (males, P<0.001; females, P = 0.8). Low ER alpha level was linked to a higher reintervention rate (P = 0.001) and earlier reintervention (P = 0.004) in male patients only (females, P = 0.95 and P = 0.65, respectively). Absence of ER alpha together with age provided a good prediction model for reintervention in male patients with gonadotroph adenomas. Conclusions: SSTR3 is expressed abundantly in NFPAs and is therefore a possible target for medical treatment. Absence of ER alpha together with young age may predict tumor recurrence in groups of NFPAs. Further validation in systematic prospective studies is needed.
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| 583. |
- Palming, Jenny, 1975, et al.
(författare)
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The expression of NAD(P)H:quinone oxidoreductase 1 is high in human adipose tissue, reduced by weight loss, and correlates with adiposity, insulin sensitivity, and markers of liver dysfunction.
- 2007
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:6, s. 2346-52
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: We have previously identified nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1 (NQO1), an enzyme involved in the protection against oxidative stress, as a gene predominantly expressed in human adipocytes. Studies in mice deficient in NQO1 activity suggest that NQO1 may also play an important role in metabolism. OBJECTIVE: The aim of this study was to explore the expression and regulation of NQO1 in human adipose tissue (AT) and isolated adipocytes. PATIENTS AND RESULTS: The high expression of NQO1 in adipocytes was verified in human adipocytes and AT by real-time PCR. DNA microarray analysis showed that NQO1 was expressed at higher levels in large compared with small adipocytes, isolated from the same fat biopsy. Furthermore, NQO1 mRNA levels were positively correlated with adipocyte size (n = 7; P < 0.002). During an 18-wk diet regime (n = 24; mean weight loss 27 kg), the NQO1 expression in human sc AT was down-regulated (P < 0.0001), and mRNA levels correlated with body mass index (P = 0.0005), sc, and total abdominal AT areas, as determined by computerized tomography (P < 0.0001, both) and metabolic parameters. NQO1 mRNA levels were also positively correlated with aspartate aminotransferase (P = 0.0028) and alanine aminotransferase (P = 0.0219), markers known to be associated with severity of hepatic steatosis. CONCLUSIONS: NQO1 is highly expressed in human AT, particularly in large adipocytes. AT NQO1 expression is reduced during diet-induced weight loss, and the expression levels positively correlate with adiposity, glucose tolerance, and markers of liver dysfunction. Together, these findings indicate a role for NQO1 in the metabolic complications of human obesity.
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| 584. |
- Papakokkinou, Eleni, et al.
(författare)
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Excess Morbidity Persists in Patients With Cushing’s Disease During Long-term Remission : A Swedish Nationwide Study
- 2020
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - Washington : Oxford University Press. - 0021-972X .- 1945-7197. ; 105:8, s. 2616-2624
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Tidskriftsartikel (refereegranskat)abstract
- Context: Whether multisystem morbidity in Cushing's disease (CD) remains elevated during long-term remission is still undetermined.Objective: To investigate comorbidities in patients with CD.Design, setting, and patients: A retrospective, nationwide study of patients with CD identified in the Swedish National Patient Register between 1987 and 2013. Individual medical records were reviewed to verify diagnosis and remission status.Main outcomes: Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by using the Swedish general population as reference. Comorbidities were investigated during three different time periods: (i) during the 3 years before diagnosis, (ii) from diagnosis to 1 year after remission, and (iii) during long-term remission.Results: We included 502 patients with confirmed CD, of whom 419 were in remission for a median of 10 (interquartile range 4 to 21) years. SIRs (95% CI) for myocardial infarction (4.4; 1.2 to 11.4), fractures (4.9; 2.7 to 8.3), and deep vein thrombosis (13.8; 3.8 to 35.3) were increased during the 3-year period before diagnosis. From diagnosis until 1 year after remission, SIRs (95% CI were increased for thromboembolism (18.3; 7.9 to 36.0), stroke (4.9; 1.3 to 12.5), and sepsis (13.6; 3.7 to 34.8). SIRs for thromboembolism (4.9; 2.6 to 8.4), stroke (3.1; 1.8 to 4.9), and sepsis (6.0; 3.1 to 10.6) remained increased during long-term remission.Conclusion: Patients with CD have an increased incidence of stroke, thromboembolism, and sepsis even after remission, emphasizing the importance of early identification and management of risk factors for these comorbidities during long-term follow-up.
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| 585. |
- Parkinson, Craig, et al.
(författare)
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Gender, body weight, disease activity, and previous radiotherapy influence the response to pegvisomant
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 92:1, s. 190-195
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Tidskriftsartikel (refereegranskat)abstract
- Context/Objective: To effectively normalize IGF-I in patients with acromegaly, various covariates may affect dosing and plasma concentrations of pegvisomant. We assessed whether sex, age, weight, and previous radiotherapy influence dosing of pegvisomant in patients with active disease. Design: Data from 69 men and 49 women participating in multicenter, open-label trials of pegvisomant were retrospectively evaluated using multiple regression techniques. Sixty-nine subjects ( 39 men, 30 women) had undergone external beam pituitary radiotherapy. Serum IGF- I was at least 30% above age- related upper limit of normal in all patients at study entry. After a loading dose of pegvisomant ( 80 mg), patients were commenced on 10 mg/d. Pegvisomant dose was adjusted by 5 mg every eighth week until serum IGF- I was normalized. Results: At baseline, men had significantly higher mean serum IGF- I levels than women despite similar GH levels. After treatment with pegvisomant, IGF- I levels were similar in men and women. A significant correlation between baseline GH, IGF- I, body weight, and the dose of pegvisomant required to normalize serum IGF- I was observed ( all P < 0.001). Women required an average of 0.04 mg/ kg more pegvisomant than men and a mean weight- corrected dose of 19.2 mg/ d to normalize serum IGF-I [14.5 mg/d ( men); P < 0.001]. Patients treated with radiotherapy required less pegvisomant to normalize serum IGF- I despite similar baseline GH/ IGF-I levels ( 15.2 vs. 18.5 mg/ d for no previous radiotherapy; P < 0.002). Conclusions: Sex, body weight, previous radiotherapy, and baseline GH/ IGF- I influence the dose of pegvisomant required to normalize serum IGF- I in patients with active acromegaly.
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| 586. |
- Paternoster, L, et al.
(författare)
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OPG and RANK Polymorphisms Are Both Associated with Cortical Bone Mineral Density: Findings from a Metaanalysis of the Avon Longitudinal Study of Parents and Children and Gothenburg Osteoporosis and Obesity Determinants Cohorts.
- 2010
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Ingår i: The journal of clinical endocrinology and metabolism. - 1945-7197. ; 95:8, s. 3940-3948
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Tidskriftsartikel (refereegranskat)abstract
- Context: Several single-nucleotide polymorphisms (SNPs) have been reliably associated with areal bone mineral density (aBMD) in genome-wide association studies of mostly older subjects. Objective: We aimed to test those SNPs for an association with peripheral quantitative computed tomography (pQCT) bone measures in two young cohorts. Design and Study Participants: We genotyped nine SNPs from the most promising aBMD candidates in a cohort of 15-yr-olds [in the Avon Longitudinal Study of Parents and Children (ALSPAC)] and carried out association analysis with several tibial pQCT measures to determine whether these candidates were important during adolescent growth and which particular skeletal parameters each of the candidates were acting upon. We also carried out a metaanalysis of the SNPs for association with cortical bone mineral density (BMDC) in ALSPAC and a similar male-only study (Gothenburg Osteoporosis and Obesity Determinants). Results: In the ALSPAC cohort, we found a significant association between RANK SNP (rs3018362) and BMDC but not any of the other pQCT bone measures. In the metaanalysis, we found the OPG SNP (rs4355801) and the RANK SNP (rs3018362) to be significantly associated with BMDC. We also found suggestive evidence of an association between the MARK3 SNP (rs2010281) and BMDC but with a direction of effect opposite to that previously reported. Conclusion: The association of genes from the RANK/RANKL/OPG pathway and BMDC provides new insight into how this system might affect the skeleton, confirming it to be associated with volumetric cortical bone density but observing no relationship with bone size.
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| 587. |
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| 588. |
- Paulsson, Johan O., et al.
(författare)
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Whole-genome Sequencing of Follicular Thyroid Carcinomas Reveal Recurrent Mutations in MicroRNA Processing Subunit DGCR8
- 2021
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 106:11, s. 3265-3282
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Tidskriftsartikel (refereegranskat)abstract
- Background: The genomic and transcriptomic landscape of widely invasive follicular thyroid carcinomas (wiFTCs) and Hurthle cell carcinoma (HCC) are poorly characterized, and subsets of these tumors lack information on genetic driver events.Objective: The aim of this study was to bridge this gap.Methods: We performed whole-genome and RNA sequencing and subsequent bioinformatic analyses of 11 wiFTCs and 2 HCCs with a particularly poor prognosis, and matched normal tissue.Results: All wiFTCs exhibited one or several mutations in established thyroid cancer genes, including TERT (n=4), NRAS (n=3), HRAS, KRAS, AKT, PTEN, PIK3CA, MUTYH, TSHR, and MEN1 (n=1 each). MutSig2CV analysis revealed recurrent somatic mutations in FAM72D (n=3, in 2 wiFTCs and in a single HCC), TP53 (n=3, in 2 wiFTCs and a single HCC), and EIF1AX (n=3), with DGCR8 (n=2) as borderline significant. The DGCR8 mutations were recurrent p.E518K missense alterations, known to cause familial multinodular goiter via disruption of microRNA (miRNA) processing. Expression analyses showed reduced DGCR8 messenger RNA expression in FTCs in general, and the 2 DGCR8 mutants displayed a distinct miRNA profile compared to DGCR8 wild-types. Copy number analyses revealed recurrent gains on chromosomes 4, 6, and 10, and fusion gene analyses revealed 27 high-quality events. Both HCCs displayed hyperploidy, which was fairly unusual in the FTC cohort. Based on the transcriptome data, tumors amassed in 2 principal clusters.Conclusion: We describe the genomic and transcriptomic landscape in wiFTCs and HCCs and identify novel recurrent mutations and copy number alterations with possible driver properties and lay the foundation for future studies.
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| 589. |
- Peddinti, Gopal, et al.
(författare)
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1-Hour Post-OGTT Glucose Improves the Early Prediction of Type 2 Diabetes by Clinical and Metabolic Markers
- 2019
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 104:4, s. 1131-1140
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Early prediction of dysglycemia is crucial to prevent progression to type 2 diabetes. The 1-hour postload plasma glucose (PG) is reported to be a better predictor of dysglycemia than fasting plasma glucose (FPG), 2-hour PG, or glycated hemoglobin (HbA1c). OBJECTIVE: To evaluate the predictive performance of clinical markers, metabolites, HbA1c, and PG and serum insulin (INS) levels during a 75-g oral glucose tolerance test (OGTT). DESIGN AND SETTING: We measured PG and INS levels at 0, 30, 60, and 120 minutes during an OGTT in 543 participants in the Botnia Prospective Study, 146 of whom progressed to type 2 diabetes within a 10-year follow-up period. Using combinations of variables, we evaluated 1527 predictive models for progression to type 2 diabetes. RESULTS: The 1-hour PG outperformed every individual marker except 30-minute PG or mannose, whose predictive performances were lower but not significantly worse. HbA1c was inferior to 1-hour PG according to DeLong test P value but not false discovery rate. Combining the metabolic markers with PG measurements and HbA1c significantly improved the predictive models, and mannose was found to be a robust metabolic marker. CONCLUSIONS: The 1-hour PG, alone or in combination with metabolic markers, is a robust predictor for determining the future risk of type 2 diabetes, outperforms the 2-hour PG, and is cheaper to measure than metabolites. Metabolites add to the predictive value of PG and HbA1c measurements. Shortening the standard 75-g OGTT to 1 hour improves its predictive value and clinical usability.
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| 590. |
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