The Enlarging List of Phenotypic Characteristics That Might Allow the Clinical Identification of Families at Risk for Type 1 Diabetes

Type 1 diabetes is a chronic metabolic disease whose aetiology and pathogenesis remain not completely understood. Most diabetic cases are complex diseases resulting from interactions between genetic and environmental determinants in genetically predisposed individuals. Genome-wide association studies allowed understanding a genetic architecture of many genetic loci with many variants of small effect. Hence, genetic risk modelling to derive prediction of individual risk and risk to relatives are difficult to reconcile. Testing for multiple antibodies can individuate individuals at very high risk for autoimmune type 1 diabetes with good sensitivity. However, currently no intervention can effectively prevent or delay diabetes, and awareness of risk is useless or even stressful. Moreover, both genetic risk and serum autoantibody profiling are uneconomical when applied in the general population. Over the years, our research efforts have sought primarily to gain a comprehensive understanding of the common phenotypic elements that characterise families with a sporadic case of type 1 diabetes. The chapter provides a research-based overview of these familial peculiarities that include multifaceted, easily detectable, clinical perturbations: physical (BMI), cardiovascular (blood pressure response to exercise and circadian blood pressure pattern), biochemical (fasting plasma glucose, HbA1c, lipids, homeostasis model assessment of insulin sensitivity, plasma markers of oxidative damage), cellular (cellular markers of oxidative damage, transplasma membrane electron transport systems, mirochondrial membrane potential), and immunological (lymphocyte subsets). First question: may insulin-resistance be their common denominator? Therefore, second question: could an early correction of one/some of these common clinical abnormalities modify the natural history of the disease and thence its epidemiology? A proper (more realistic) public health intervention (by general and family practitioners) should be designed beyond the conventional boundaries that have for so long limited the visual field

Electron Pathways through Erythrocyte Plasma Membrane in Human Physiology and Pathology: Potential Redox Biomarker?

Erythrocytes are involved in the transport of oxygen and carbon dioxide in the body. Since pH is the influential factor in the Bohr-Haldane effect, pHi is actively maintained via secondary active transports Na+/H+ exchange and HC3−/Cl− anion exchanger. Because of the redox properties of the iron, hemoglobin generates reactive oxygen species and thus, the human erythrocyte is constantly exposed to oxidative damage. Although the adult erythrocyte lacks protein synthesis and cannot restore damaged proteins, it is equipped with high activity of protective enzymes. Redox changes in the cell initiate various signalling pathways. Plasma membrane oxido-reductases (PMORs) are transmembrane electron transport systems that have been found in the membranes of all cells and have been extensively characterized in the human erythrocyte. Erythrocyte PMORs transfer reducing equivalents from intracellular reductants to extracellular oxidants, thus their most important role seems to be to enable the cell respond to changes in intra- and extra-cellular redox environments

The point-of-care testing in diabetology

In diabetic patients glucose, haemoglobin A1c, ketones, lipids, and urinary albumin monitoring allows prevention, early detection, and treatment of diabetes-related acute and chronic complications. The point-of-care testing (PoCT) technology offers convenient aspects, as long as pre-analytical, analytical, and post-analytical errors are minimised. The overview summarises the current state-of-the-art of PoCT in diabetes care

Barley beta-glucan promotes MnSOD expression and enhances angiogenesis under oxidative microenvironment

Manganese superoxide dismutase (MnSOD), a foremost antioxidant enzyme, plays a key role in angiogenesis. Barley-derived (1.3) β-D-glucan (β-D-glucan) is a natural water-soluble polysaccharide with antioxidant properties. To explore the effects of β-D-glucan on MnSOD-related angiogenesis under oxidative stress, we tested epigenetic mechanisms underlying modulation of MnSOD level in human umbilical vein endothelial cells (HUVECs) and angiogenesis in vitro and in vivo. Long-term treatment of HUVECs with 3% w/v β-D-glucan significantly increased the level of MnSOD by 200±2% compared to control and by 50±4% compared to untreated H2O2-stressed cells. β-D-glucan-treated HUVECs displayed greater angiogenic ability. In vivo, 24h-treatment with 3% w/v β-D-glucan rescued vasculogenesis in Tg (kdrl: EGFP) s843Tg zebrafish embryos exposed to oxidative microenvironment. HUVECs overexpressing MnSOD demonstrated an increased activity of endothelial nitric oxide synthase (eNOS), reduced load of superoxide anion (O2-) and an increased survival under oxidative stress. In addition, β-D-glucan prevented the rise of hypoxia inducible factor (HIF)1-α under oxidative stress. The level of histone H4 acetylation was significantly increased by β-D-glucan. Increasing histone acetylation by sodium butyrate, an inhibitor of class I histone deacetylases (HDACs I), did not activate MnSOD-related angiogenesis and did not impair β-D-glucan effects. In conclusion, 3% w/v β-D-glucan activates endothelial expression of MnSOD independent of histone acetylation level, thereby leading to adequate removal of O2-, cell survival and angiogenic response to oxidative stress. The identification of dietary β-D-glucan as activator of MnSOD-related angiogenesis might lead to the development of nutritional approaches for the prevention of ischemic remodeling and heart failure

Insulin administration: present strategies and future directions for a noninvasive (possibly more physiological) delivery

nsulin is a life-saving medication for people with type 1 diabetes, but traditional insulin replacement therapy is based on multiple daily subcutaneous injections or continuous subcutaneous pump-regulated infusion. Nonphysiologic delivery of subcutaneous insulin implies a rapid and sustained increase in systemic insulin levels due to the loss of concentration gradient between portal and systemic circulations. In fact, the liver degrades about half of the endogenous insulin secreted by the pancreas into the venous portal system. The reverse insulin distribution has short- and long-term effects on glucose metabolism. Thus, researchers have explored less-invasive administration routes based on innovative pharmaceutical formulations, which preserve hormone stability and ensure the therapeutic effectiveness. This review examines some of the recent proposals from clinical and material chemistry point of view, giving particular attention to patients' (and diabetologists') ideal requirements that organic chemistry could meet

Regulatory T Cells with Effector Memory Phenotype and Glycaemic Control in Adult Type 1 Diabetes Mellitus

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Clinical Efficacy of A Nutraceutical Approach for the Management of Dyslipidemia in Metabolic Disorders: A One-Year Treatment With Armolipid Plus

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Pleiotropic and potentially beneficial effects of reactive oxygen species on the intracellular signaling pathways in endothelial cells

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Endothelial cells (ECs) are exposed to molecular dioxygen and its derivative reactive oxygen species (ROS). ROS are now well established as important signaling messengers. Excessive production of ROS, however, results in oxidative stress, a significant contributor to the development of numerous diseases. Here, we analyze the experimental data and theoretical concepts concerning positive pro-survival effects of ROS on signaling pathways in endothelial cells (ECs). Our analysis of the available experimental data suggests possible positive roles of ROS in induction of pro-survival pathways, downstream of the Gi-protein-coupled receptors, which mimics insulin signaling and prevention or improvement of the endothelial dysfunction. It is, however, doubtful, whether ROS can contribute to the stabilization of the endothelial barrier.info:eu-repo/semantics/publishedVersio