1,721,011 research outputs found
The ABA/LANCL Hormone/Receptor System in the Control of Glycemia, of Cardiomyocyte Energy Metabolism, and in Neuroprotection: A New Ally in the Treatment of Diabetes Mellitus?
No full textAbscisic acid (ABA), long known as a plant stress hormone, is present and functionally active in organisms other than those pertaining to the land plant kingdom, including cyanobacteria, fungi, algae, protozoan parasites, lower Metazoa, and mammals. The ancient, cross-kingdom role of this stress hormone allows ABA and its signaling pathway to control cell responses to environmental stimuli in diverse organisms such as marine sponges, higher plants, and humans. Recent advances in our knowledge about the physiological role of ABA and of its mammalian receptors in the control of energy metabolism and mitochondrial function in myocytes, adipocytes, and neuronal cells allow us to foresee therapeutic applications for ABA in the fields of pre-diabetes, diabetes, and cardio- and neuro-protection. Vegetal extracts titrated in their ABA content have shown both efficacy and tolerability in preliminary clinical studies. As the prevalence of glucose intolerance, diabetes, and cardiovascular and neurodegenerative diseases is steadily increasing in both industrialized and rapidly developing countries, new and cost-efficient therapeutics to combat these ailments are much needed to ensure disease-free aging for the current and future working generations
Ascorbic acid-pretreated quartz enhances cyclo-oxygenase-2 expression in RAW 264.7 murine macrophages
No full textExposure to quartz particles induces a pathological process named silicosis.Alveolar macrophages initiate the disease through their activation, which isthe origin of the later dysfunctions. Ascorbic acid is known to selectivelydissolve the quartz surface. During the reaction, ascorbic acid progressivelydisappears and hydroxyl radicals are generated from the quartz surface.These observations may be relevant to mammalian quartz toxicity, as sub-stantial amounts of ascorbic acid are present in the lung epithelium. Westudied the inflammatory response of the murine macrophage cell lineRAW 264.7 incubated with ascorbic acid-treated quartz, through theexpression and activity of the enzyme cyclo-oxygenase-2 (COX-2). COX-2expression and prostaglandin secretion were enhanced in cells incubatedwith ascorbic acid-treated quartz. In contrast, no changes were observed incells incubated with Aerosil OX50, an amorphous form of silica. Quantifi-cation of COX-2 mRNA showed a threefold increase in cells incubatedwith ascorbic acid-treated quartz compared with controls. The transcriptionfactors, NF-kB, pCREB and AP-1, were all implicated in the increasedinflammatory response. Reactive oxygen species (H2O2and OH•) wereinvolved in COX-2 expression in this experimental model. Parallel experi-ments performed on rat alveolar macrophages from bronchoalveolar lavageconfirmed the enhanced COX-2 expression and activity in the cells incuba-ted with ascorbic acid-treated quartz compared with untreated quartz. Inconclusion, the selective interaction with, and modification of, quartz parti-cles by ascorbic acid may be a crucial event determining the inflammatoryresponse of macrophages, which may subsequently develop into acute inflammation, eventually leading to the chronic pulmonary disease silicosis
Controlled Release of Insulin Granules from PLGA Microparticles for Glucose Modulation in Diabetes
No full textMicrogram amounts of abscisic acid in fruit extracts improve glucose tolerance and reduce insulinemia in rats and in humans
No full text2-Cis,4-trans-abscisic acid (ABA) is a plant hormone that is present also in animals. Several lines of evidence suggest that ABA contributes to the regulation of glycemia in mammals: nanomolar ABA stimulates insulin release from β-pancreatic cells and glucose transporter-4-mediated glucose uptake by myoblasts and adipocytes in vitro; plasma ABA increases in normal human subjects, but not in diabetic patients, after a glucose load for an oral glucose tolerance test (OGTT). The presence of ABA in fruits prompted an exploration of the bioavailability of dietary ABA and the effect of ABA-rich fruit extracts on glucose tolerance. Rats underwent an OGTT, with or without 1 μg/kg ABA, either synthetic or present in a fruit extract. Human volunteers underwent an OGTT or a standard breakfast and lunch, with or without a fruit extract, yielding an ABA dose of 0.85 or 0.5 μg/kg, respectively. Plasma glucose, insulin, and ABA were measured at different time points. Oral ABA at 0.5-1 μg/kg significantly lowered glycemia and insulinemia in rats and in humans. Thus, the glycemia-lowering effect of low-dose ABA in vivo does not depend on an increased insulin release. Low-dose ABA intake may be proposed as an aid to improving glucose tolerance in patients with diabetes who are deficient in or resistant to insulin.-Magnone, M., Ameri, P., Salis, A., Andraghetti, G., Emionite, L., Murialdo, G., De Flora, A., Zocchi, E. Microgram amounts of abscisic acid in fruit extracts improve glucose tolerance and reduce insulinemia in rats and in humans
Synthetic analogues of abscisic acid with anti-inflammatory and insulin release stimulation effects on human cells
No full textEstrogen-Related Receptor α: A Key Transcription Factor in the Regulation of Energy Metabolism at an Organismic Level and a Target of the ABA/LANCL Hormone Receptor System
No full textThe orphan nuclear receptor ERRα is the most extensively researched member of the estrogen-related receptor family and holds a pivotal role in various functions associated with energy metabolism, especially in tissues characterized by high energy requirements, such as the heart, skeletal muscle, adipose tissue, kidney, and brain. Abscisic acid (ABA), traditionally acknowledged as a plant stress hormone, is detected and actively functions in organisms beyond the land plant kingdom, encompassing cyanobacteria, fungi, algae, protozoan parasites, lower Metazoa, and mammals. Its ancient, cross-kingdom role enables ABA and its signaling pathway to regulate cell responses to environmental stimuli in various organisms, such as marine sponges, higher plants, and humans. Recent advancements in understanding the physiological function of ABA and its mammalian receptors in governing energy metabolism and mitochondrial function in myocytes, adipocytes, and neuronal cells suggest potential therapeutic applications for ABA in pre-diabetes, diabetes, and cardio-/neuroprotection. The ABA/LANCL1-2 hormone/receptor system emerges as a novel regulator of ERRα expression levels and transcriptional activity, mediated through the AMPK/SIRT1/PGC-1α axis. There exists a reciprocal feed-forward transcriptional relationship between the LANCL proteins and transcriptional coactivators ERRα/PGC-1α, which may be leveraged using natural or synthetic LANCL agonists to enhance mitochondrial function across various clinical contexts
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