Search results for "Transduction"
showing 10 items of 2149 documents
Hypothalamic Apelin/Reactive Oxygen Species Signaling Controls Hepatic Glucose Metabolism in the Onset of Diabetes
2014
Aims: We have previously demonstrated that central apelin is implicated in the control of peripheral glycemia, and its action depends on nutritional (fast versus fed) and physiological (normal versus diabetic) states. An intracerebroventricular (icv) injection of a high dose of apelin, similar to that observed in obese/diabetic mice, increase fasted glycemia, suggesting (i) that apelin contributes to the establishment of a diabetic state, and (ii) the existence of a hypothalamic to liver axis. Using pharmacological, genetic, and nutritional approaches, we aim at unraveling this system of regulation by identifying the hypothalamic molecular actors that trigger the apelin effect on liver gluc…
GLP-2 as Beneficial Factor in the Glucose Homeostasis in Mice Fed a High Fat Diet
2015
Glucagon like peptide-2 (GLP-2) is a gastrointestinal hormone released in response to dietary nutrients, which acts through a specific receptor, the GLP-2 receptor (GLP-2R). The physiological effects of GLP-2 are multiple, involving also the intestinal adaptation to high fat diet (HFD). In consideration of the well-known relationship between chronic HFD and impaired glucose metabolism, in the present study we examined if the blocking of the GLP-2 signaling by chronic treatment with the GLP-2R antagonist, GLP-2 (3-33), leads to functional consequences in the regulation of glucose metabolism in HFD-fed mice. Compared with animals fed standard diet (STD), mice at the 10th week of HFD showed hy…
Mechanisms involved in the relaxant action of testosterone in the renal artery from male normoglycemic and diabetic rabbits.
2009
Kidney disease is a frequent complication in diabetes, and significant differences have been reported between male and female patients. Our working hypothesis was that diabetes might modify the vascular actions of testosterone in isolated rabbit renal arteries and the mechanisms involved in these actions. Testosterone (10(-8) to 10(-4)M) induced relaxation of precontracted arteries, without significant differences between control and diabetic rabbits. Both in control and diabetic rabbits endothelium removal inhibited testosterone relaxant action. In arteries with endothelium, incubation with indomethacin (10(-5)M), N(G)-nitro-l-arginine (10(-5)M) or tetraethylammonium (10(-5)M) did not modi…
The sodium-glucose co-transporter 2 inhibitor empagliflozin improves diabetes-induced vascular dysfunction in the streptozotocin diabetes rat model b…
2014
Objective In diabetes, vascular dysfunction is characterized by impaired endothelial function due to increased oxidative stress. Empagliflozin, as a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), offers a novel approach for the treatment of type 2 diabetes by enhancing urinary glucose excretion. The aim of the present study was to test whether treatment with empagliflozin improves endothelial dysfunction in type I diabetic rats via reduction of glucotoxicity and associated vascular oxidative stress. Methods Type I diabetes in Wistar rats was induced by an intravenous injection of streptozotocin (60 mg/kg). One week after injection empagliflozin (10 and 30 mg/kg/d) was adminis…
Hydroxychloroquine, COVID ‐19 and diabetes. Why it is a different story
2020
Hydroxychloroquine has been proposed for the cure of the COVID-19 due to its anti-inflammatory and anti-viral action. People with diabetes are more prone to severe outcome if affected by COVID-19 and the use of Hydroxychloroquine might have some benefit in this setting. However, the use of Hydroxychloroquine in diabetes deserves particular attention for its documented hypoglycemic action.
The Inflammatory Role of Platelets : Translational Insights from Experimental Studies of Autoimmune Disorders
2016
Beyond their indispensable role in hemostasis, platelets have shown to affect the development of inflammatory disorders, as they have been epidemiologically and mechanistically linked to diseases featuring an inflammatory reaction in inflammatory diseases like multiple sclerosis, rheumatoid arthritis and inflammatory bowel disorders. The identification of novel molecular mechanisms linking inflammation and to platelets has highlighted them as new targets for therapeutic interventions. In particular, genetic and pharmacological studies have identified an important role for platelets in neuroinflammation. This review summarizes the main molecular links between platelets and inflammation, focu…
The Serine/Threonine Protein Phosphatase 2A (PP2A) Regulates Syk Activity in Human Platelets
2020
Distinct membrane receptors activate platelets by Src-family-kinase (SFK)-, immunoreceptor-tyrosine-based-activation-motif (ITAM)-dependent stimulation of spleen tyrosine kinase (Syk). Recently, we reported that platelet activation via glycoprotein (GP) VI or GPIb&alpha
The Neutrophil Secretome as a Crucial Link between Inflammation and Thrombosis
2021
Cardiovascular diseases are a leading cause of death. Blood–cell interactions and endothelial dysfunction are fundamental in thrombus formation, and so further knowledge of the pathways involved in such cellular crosstalk could lead to new therapeutical approaches. Neutrophils are secretory cells that release well-known soluble inflammatory signaling mediators and other complex cellular structures whose role is not fully understood. Studies have reported that neutrophil extracellular vesicles (EVs) and neutrophil extracellular traps (NETs) contribute to thrombosis. The objective of this review is to study the role of EVs and NETs as key factors in the transition from inflammation to thrombo…
Native, Intact Glucagon-Like Peptide 1 Is a Natural Suppressor of Thrombus Growth Under Physiological Flow Conditions
2020
Objective: In patients with diabetes mellitus, increased platelet reactivity predicts cardiac events. Limited evidence suggests that DPP-4 (dipeptidyl peptidase 4) influences platelets via GLP-1 (glucagon-like peptide 1)-dependent effects. Because DPP-4 inhibitors are frequently used in diabetes mellitus to improve the GLP-1-regulated glucose metabolism, we characterized the role of DPP-4 inhibition and of native intact versus DPP-4-cleaved GLP-1 on flow-dependent thrombus formation in mouse and human blood. Approach and Results: An ex vivo whole blood microfluidics model was applied to approach in vivo thrombosis and study collagen-dependent platelet adhesion, activation, and thrombus for…
The Gut Microbiota as an Influencing Factor of Arterial Thrombosis
2018
The mutualistic gut microbiota does not only impact the development and function of various immune cell types, but it also influences the function of the hepatic vascular endothelium and prothrombotic platelet function. With germ-free mouse models, we have demonstrated that gut-derived microbial-associated molecular patterns could stimulate hepatic von Willebrand factor (VWF) synthesis and plasmatic VWF levels through Toll-like receptor-2 (TLR2), thus defining the extent of platelet deposition to the subendothelial matrix of the ligation-injured common carotid artery. In addition to the microbiota-derived choline metabolite trimethylamine N-oxide and the microbiota's regulatory role on the …