Frontiers in endocrinology
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Front Endocrinol (Lausanne) · Jan 2020
Roles of Testosterone and Estradiol in Mediation of Acute Neuroendocrine and Electroencephalographic Effects of Sevoflurane During the Sensitive Period in Rats.
Testosterone (T), predominantly acting through its derivative 17β-estradiol (E2), regulates the brain's sexual differentiation in rodents during the perinatal sensitive period, which mirrors the window of vulnerability to the adverse effects of general anesthetics. The mechanisms of anesthesia's adverse effects are poorly understood. We investigated whether sevoflurane alters T and E2 levels and whether they contribute to sevoflurane's acute adverse effects in postnatal day 5 Sprague-Dawley rats. ⋯ The ERα antagonist MPP, but not the ERβ antagonist PHTPP, reduced electroencephalography-detectable seizures and normalized the Nkcc1/Kcc2 mRNA ratio. Collectively, sevoflurane exacerbates levels of T in males and E2 in both sexes during the period of their organizational effects in rodents. Sevoflurane acts through GABAAR-mediated, systemic T-independent elevation of E2 to cause electroencephalography-detectable seizures, stress-like corticosterone secretion, and changes in the expression of genes critical for brain development.
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Front Endocrinol (Lausanne) · Jan 2020
Left Heart Dysfunction in Acromegaly Revealed by Novel Echocardiographic Methods.
Background: Acromegaly is a rare disease that requires modern treatment to decrease the risk of mortality, mainly from vascular diseases. Identifying acromegalic patients with increased cardiovascular risk is challenging. Speckle-tracking echocardiography (STE) is a modern, well-validated, and reproducible method of assessing left ventricular longitudinal deformation and providing a sensitive assessment of myocardial contractility. ⋯ Results: The ACRO group, compared to the CONTROL group, presented: (1) higher left ventricular mass (left ventricular mass index: 132 vs. 108 g/m2, p < 0.001) and, in consequence, more frequent LV hypertrophy (80.0 vs. 53.3%; p = 0.028); (2) impaired LV systolic function measured by both left ventricular ejection fraction (LVEF) (63.4 vs. 66.9%, p < 0.001) and global longitudinal strain (GLS) (-18.1 vs. -19.4%, p = 0.023); (3) greater LA anteroposterior diameter (40.3 vs. 36.9 mm, p = 0.003) and indexed left atrial volume (37.9 vs. 27.6 ml/m2, p < 0.001); and (4) impaired echocardiographic strain parameters corresponding with LA function. Conclusions: Acromegaly, even in young patients with good blood pressure control, may be associated with left ventricular hypertrophy and subclinical impairment of the left ventricular and left atrial mechanical function, which may be identified by speckle-tracking echocardiography. Further research in this area is necessary to clarify the prognostic value of these phenomena.
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Front Endocrinol (Lausanne) · Jan 2020
Tautomerase Activity-Lacking of the Macrophage Migration Inhibitory Factor Alleviates the Inflammation and Insulin Tolerance in High Fat Diet-Induced Obese Mice.
Macrophage migration inhibitory factor (MIF) has multiple intrinsic enzymatic activities of the dopachrome/phenylpyruvate tautomerase and thiol protein oxidoreductase, and plays an important role in the development of obesity as a pro-inflammatory cytokine. However, which enzymatic activity of MIF is responsible for regulating in obesity are still unknown. In the present study, we investigated the roles of the tautomerase of MIF in high fat diet (HFD)-induced obesity using MIF tautomerase activity-lacking (MIFP1G/P1G) mice. ⋯ The glucose tolerance tests (GTT) and insulin tolerance tests (ITT) assays showed that the glucose tolerance and insulin resistance were markedly improved, and the expressions of IRS and PPARγ were upregulated in adipose tissue from MIFP1G/P1G mice fed with HFD. Furthermore, we observed that the expressions of Bax, a pro-apoptotic protein, and the cleaved caspase 3-positive cells in white tissues were decreased and the ratio of Bcl2/Bax was increased in MIFP1G/P1G mice compared with WT mice. Taken together, our results demonstrated that the tautomerase activity-lacking of MIF significantly alleviated the HFD-induced obesity and adipose tissue inflammation, and improved insulin resistance in MIFP1G/P1G mice.
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Front Endocrinol (Lausanne) · Jan 2019
ReviewThe Discovery and Development of Liraglutide and Semaglutide.
The discovery of glucagon-like peptide-1 (GLP-1), an incretin hormone with important effects on glycemic control and body weight regulation, led to efforts to extend its half-life and make it therapeutically effective in people with type 2 diabetes (T2D). The development of short- and then long-acting GLP-1 receptor agonists (GLP-1RAs) followed. Our article charts the discovery and development of the long-acting GLP-1 analogs liraglutide and, subsequently, semaglutide. ⋯ In summary, rational design has led to the development of two long-acting GLP-1 analogs, liraglutide and semaglutide, that have made a vast contribution to the management of T2D in terms of improvements in glycemic control, body weight, blood pressure, lipids, beta-cell function, and CV outcomes. Furthermore, the development of an oral formulation for semaglutide may provide individuals with additional benefits in relation to treatment adherence. In addition to T2D, liraglutide is used in the treatment of obesity, while semaglutide is currently under investigation for use in obesity and NASH.
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Front Endocrinol (Lausanne) · Jan 2019
Use of Non-invasive Parameters and Machine-Learning Algorithms for Predicting Future Risk of Type 2 Diabetes: A Retrospective Cohort Study of Health Data From Kuwait.
Objective: In recent decades, the Arab population has experienced an increase in the prevalence of type 2 diabetes (T2DM), particularly within the Gulf Cooperation Council. In this context, early intervention programmes rely on an ability to identify individuals at risk of T2DM. We aimed to build prognostic models for the risk of T2DM in the Arab population using machine-learning algorithms vs. conventional logistic regression (LR) and simple non-invasive clinical markers over three different time scales (3, 5, and 7 years from the baseline). ⋯ For all models, the discriminatory power decreased as the prediction horizon increased from 3 to 7 years. Conclusions: Machine-learning techniques represent a useful addition to the commonly reported LR technique. Our prognostic models for the future risk of T2DM could be used to plan and implement early prevention programmes for at risk groups in the Arab population.