المؤلفون: Carlos Fernández-Fernández, María M. Adeva-Andany, Natalia Carneiro-Freire, Raquel Funcasta-Calderón, Elvira Castro-Quintela

المصدر: Journal of Clinical & Translational Endocrinology
Journal of Clinical & Translational Endocrinology, Vol 15, Iss, Pp 45-53 (2019)

مصطلحات موضوعية: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, T2D, type 2 diabetes, 030209 endocrinology & metabolism, Review, Type 2 diabetes, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Glucagon, Impaired glucose tolerance, Animal protein, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin resistance, Internal medicine, Diabetes mellitus, BCAA, branched-chain amino acid, Medicine, 030212 general & internal medicine, Type 1 diabetes, lcsh:RC648-665, business.industry, Insulin, Diabetes, Glucagon secretion, Cardiovascular risk, medicine.disease, SGLT2, sodium-glucose co-transporter-2, T1D, type 1 diabetes, business, Vegetable protein

الوصف: Diabetes is a common metabolic disorder that involves glucose, amino acids, and fatty acids. Either insulin deficiency or insulin resistance may cause diabetes. Insulin deficiency causes type 1 diabetes and diabetes associated with total pancreatectomy. Glucagon produces insulin resistance. Glucagon-induced insulin resistance promotes type 2 diabetes and diabetes associated with glucagonoma. Further, glucagon-induced insulin resistance aggravates the metabolic consequences of the insulin-deficient state. A major metabolic effect of insulin is the accumulation of glucose as glycogen in the liver. Glucagon opposes hepatic insulin action and enhances the rate of gluconeogenesis, increasing hepatic glucose output. In order to support gluconeogenesis, glucagon promotes skeletal muscle wasting to supply amino acids as gluconeogenic precursors. Glucagon promotes hepatic fatty acid oxidation to supply energy required to sustain gluconeogenesis. Hepatic fatty acid oxidation generates β-hydroxybutyrate and acetoacetate (ketogenesis). Prospective studies reveal that elevated glucagon secretion at baseline occurs in healthy subjects who develop impaired glucose tolerance at follow-up compared with subjects who maintain normal glucose tolerance, suggesting a relationship between elevated glucagon secretion and development of impaired glucose tolerance. Prospective studies have identified animal protein consumption as an independent risk factor for type 2 diabetes and cardiovascular disease. Animal protein intake activates glucagon secretion inducing sustained elevations in plasma glucagon. Glucagon is a major hormone that causes insulin resistance. Insulin resistance is an established cardiovascular risk factor additionally to its pathogenic role in diabetes. Glucagon may be a potential link between animal protein intake and the risk of developing type 2 diabetes and cardiovascular disease. Keywords: Animal protein, Vegetable protein, Insulin resistance, Impaired glucose tolerance, Diabetes, Cardiovascular risk, Glucagon

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e9354c569bba1c123e0224e8648b700Test
https://doi.org/10.1016/j.jcte.2018.12.005Test

المؤلفون: Alessandra Eva, Paola Marcolongo, Roberta Resaz, Chiara Lavarello, Simonetta Astigiano, Maria Veiga-da-Cunha, Daniela Melis, Federica Raggi, Antonia Assunto, Andrea Petretto, Alessandra Gamberucci, Maria Carla Bosco, Daniela Segalerba, Francesco Trepiccione, Mariavittoria D'Acierno

المساهمون: Resaz, R., Raggi, F., Segalerba, D., Lavarello, C., Gamberucci, A., Bosco, M. C., Astigiano, S., Assunto, A., Melis, D., D'Acierno, M., Veiga-da-Cunha, M., Petretto, A., Marcolongo, P., Trepiccione, F., Eva, A.

المصدر: Molecular Genetics and Metabolism Reports, Vol 29, Iss, Pp 100813-(2021)
Molecular Genetics and Metabolism Reports

مصطلحات موضوعية: G-CSF, granulocyte colony stimulating factor, Medicine (General), Neutrophils, 1,5AG, 1,5-anhydroglucitol, Pharmacology, Inflammatory bowel disease, chemistry.chemical_compound, CFU, colony forming units, Endocrinology, 1,5-anhydroglucitol-6-phosphate, 5-anhydroglucitol-6-phosphate, NET, neutrophil extracellular trap, PRM, parallel reaction monitoring, GSDIb, Glycogen Storage Disease type 1b, Medicine, Glycogen storage disease, Dapagliflozin, Biology (General), 1,5AG6P, 1,5-anhydroglucitol-6-phosphate, M-CSF, macrophage colony stimulating factor, Metabolic disorder, Neutrophil, Genetic disorder, Glucose analog, PMA, phorbol myristate acetate, Renal sodium-glucose co-transporter-2, SGLT2 Inhibitor, Glycogen storage disease type 1b, QH301-705.5, Short Communication, Neutropenia, Mouse model, R5-920, b15-anhydroglucitol-6-phosphate, Genetics, G6PC3, glucose-6-phosphatase C3, Molecular Biology, TM, tamoxifen, business.industry, medicine.disease, fMLP, N-formyl-L-methionyl-L-leucyl-phenylalanine, SGLT2, sodium-glucose co-transporter-2, chemistry, Glycogen storage disease type 1, BM, bone marrow, G6PT, glucose-6-phospate translocase, business

الوصف: Glycogen Storage Disease type 1b (GSDIb) is a genetic disorder with long term severe complications. Accumulation of the glucose analog 1,5-anhydroglucitol-6-phosphate (1,5AG6P) in neutrophils inhibits the phosphorylation of glucose in these cells, causing neutropenia and neutrophil dysfunctions. This condition leads to serious infections and inflammatory bowel disease (IBD) in GSDIb patients. We show here that dapagliflozin, an inhibitor of the renal sodium-glucose co-transporter-2 (SGLT2), improves neutrophil function in an inducible mouse model of GSDIb by reducing 1,5AG6P accumulation in myeloid cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d2a972cc08490cef934144a4ec91b7f7Test
http://hdl.handle.net/11386/4803796Test

المؤلفون: Giacomo Germani, Chiara Becchetti, Patrizia Burra

المصدر: Burra, Patrizia; Becchetti, Chiara; Germani, Giacomo (2020). NAFLD and liver transplantation: Disease burden, current management and future challenges. JHEP reports, 2(6), p. 100192. Elsevier 10.1016/j.jhepr.2020.100192 <http://dx.doi.org/10.1016/j.jhepr.2020.100192Test>
JHEP Reports

مصطلحات موضوعية: medicine.medical_treatment, Review, Disease, Liver transplantation, DPP-4, dipeptidyl peptidase-4, Solid organ transplantation, GLP1 RAs, glucagon-like peptide-1 receptor agonists, mTORi, mammalian target of rapamycin inhibitors, DM, diabetes mellitus, MAFLD, metabolic dysfunction-associated fatty liver disease, Immunology and Allergy, 610 Medicine & health, Non-alcoholic steatohepatitis, Immunosuppressant, Metabolic complication, Fatty liver, Gastroenterology, Graft survival, Immunosuppression, Hypertension, NAFLD, non-alcoholic fatty liver disease, medicine.medical_specialty, NASH, non-alcoholic steatohepatitis, IRR, incidence rate ratio, Diabetes mellitus, Internal Medicine, medicine, Obesity, CNI, calcineurin inhibitors, Intensive care medicine, Disease burden, UNOS, United Network for Organ Sharing, Hepatology, business.industry, CKD, chronic kidney disease, ELTR, European Liver Transplant Registry, Odds ratio, medicine.disease, HR, hazard ratio, SGLT2, sodium-glucose co-transporter-2, OR, odds ratio, ESLD, end-stage liver disease, New-onset diabetes after transplantation, Patient survival, Steatohepatitis, HCC, hepatocellular carcinoma, business, LT, liver transplant, Non-alcoholic fatty liver disease

الوصف: Summary Non-alcoholic fatty liver disease (NAFLD), specifically its progressive form non-alcoholic steatohepatitis (NASH), represents the fastest growing indication for liver transplantation in Western countries. Diabetes mellitus, morbid obesity and cardiovascular disease are frequently present in patients with NAFLD who are candidates for liver transplantation. These factors require specific evaluation, including a detailed pre-surgical risk stratification, in order to improve outcomes after liver transplantation. Moreover, in the post-transplantation setting, the incidence of cardiovascular events and metabolic complications can be amplified by immunosuppressive therapy, which is a well-known driver of metabolic alterations. Indeed, patients with NASH are more prone to developing early post-transplant complications and, in the long-term, de novo malignancy and cardiovascular events, corresponding to higher mortality rates. Therefore, a tailored multidisciplinary approach is required for these patients, both before and after liver transplantation. Appropriate candidate selection, lifestyle modifications and specific assessment in the pre-transplant setting, as well as pharmacological strategies, adjustment of immunosuppression and a healthy lifestyle in the post-transplant setting, play a key role in correct management.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5b92b01a96954af5a17961262b54974fTest

المؤلفون: Karl J. Lackner, Siyer Roohani, Maximilian Kopp, Philipp Welschof, Serge P. Bottari, Andreas Daiber, Matthias Oelze, Philip Wenzel, Ning Xia, Ute Gödtel-Armbrust, Eric Mayoux, Huige Li, Leszek Wojnowski, Thomas Münzel, Swenja Kröller-Schön, Sebastian Steven, Alina Hanf, Eberhard Schulz, Fatemeh Kashani

المصدر: Redox Biology
Redox Biology, Vol 13, Iss C, Pp 370-385 (2017)

مصطلحات موضوعية: Male, 0301 basic medicine, endocrine system diseases, Diabetic Cardiomyopathies, FPS-ZM1, RAGE inhibitor, Clinical Biochemistry, Aorta, Thoracic, RAGE, receptor for AGE, ICAM-1, intercellular adhesion molecule-1, ECL, enhanced chemiluminescence, 030204 cardiovascular system & hematology, DPP-4, dipeptidyl peptidase-4, medicine.disease_cause, TNF-α, tumor necrosis factor-α, Biochemistry, eNOS, endothelial •NO synthase (type 3), 0302 clinical medicine, Glucosides, ecSOD, extracellular superoxide dismutase, Insulin-Secreting Cells, CCL-2, see MCP-1, Hyperlipidemia, Hyperinsulinemia, GTN, glyceryl trinitrate (nitroglycerin), IFN-γ, interferon-γ, DHE, dihydroethidine, Endothelial dysfunction, IL-6, interleukin-6, lcsh:QH301-705.5, HO-1, heme oxygenase-1, lcsh:R5-920, ICAM-1, NG, normoglycemia, Diabetes, Nox, catalytic subunit of NADPH oxidase, SGLT2 inhibitor, β-cell content, L-012, 8-amino-5-chloro-7-phenylpyrido[3,4-d]pyridazine-1,4-(2H,3H)dione sodium salt, ChIP, chromatin immunoprecipitation, C-Reactive Protein, CRP, C-reactive protein, AGE, advanced glycation end products, HbA1c, glycohemoglobin, lcsh:Medicine (General), Research Paper, Zucker diabetic fatty rats, medicine.medical_specialty, DMSO, dimethylsulfoxide, MCP-1, monocyte-chemoattractant-protein-1, qRT-PCR, quantitative reverse transcription polymerase chain reaction, ZDF, Zucker diabetic fatty (rat), Low-grade inflammation, 03 medical and health sciences, ROS, reactive oxygen species, Sodium-Glucose Transporter 2, Physiology (medical), Internal medicine, Diabetes mellitus, PKC, protein kinase C, Empagliflozin, medicine, Animals, Hypoglycemic Agents, Benzhydryl Compounds, COX2, cyclooxygenase-2, SGLT2i, SGLT2 inhibitor, Sodium-Glucose Transporter 2 Inhibitors, Glycated Hemoglobin, ACh, acetylcholine, business.industry, Organic Chemistry, nutritional and metabolic diseases, Type 2 Diabetes Mellitus, medicine.disease, H2K9me2, histone3 lysine9 dimethylation, Rats, Rats, Zucker, DHFR, dihydrofolate reductase, SGLT2, sodium-glucose co-transporter-2, Oxidative Stress, sGC, soluable guanylyl cyclase, Glucose, 030104 developmental biology, Endocrinology, lcsh:Biology (General), ALDH-2, mitochondrial aldehyde dehydrogenase, Endothelium, Vascular, AGE/RAGE signaling, HG, hyperglycemia, business, Oxidative stress

الوصف: Hyperglycemia associated with inflammation and oxidative stress is a major cause of vascular dysfunction and cardiovascular disease in diabetes. Recent data reports that a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), empagliflozin (Jardiance®), ameliorates glucotoxicity via excretion of excess glucose in urine (glucosuria) and significantly improves cardiovascular mortality in type 2 diabetes mellitus (T2DM). The overarching hypothesis is that hyperglycemia and glucotoxicity are upstream of all other complications seen in diabetes. The aim of this study was to investigate effects of empagliflozin on glucotoxicity, β-cell function, inflammation, oxidative stress and endothelial dysfunction in Zucker diabetic fatty (ZDF) rats. Male ZDF rats were used as a model of T2DM (35 diabetic ZDF‐Leprfa/fa and 16 ZDF-Lepr+/+ controls). Empagliflozin (10 and 30 mg/kg/d) was administered via drinking water for 6 weeks. Treatment with empagliflozin restored glycemic control. Empagliflozin improved endothelial function (thoracic aorta) and reduced oxidative stress in the aorta and in blood of diabetic rats. Inflammation and glucotoxicity (AGE/RAGE signaling) were epigenetically prevented by SGLT2i treatment (ChIP). Linear regression analysis revealed a significant inverse correlation of endothelial function with HbA1c, whereas leukocyte-dependent oxidative burst and C-reactive protein (CRP) were positively correlated with HbA1c. Viability of hyperglycemic endothelial cells was pleiotropically improved by SGLT2i. Empagliflozin reduces glucotoxicity and thereby prevents the development of endothelial dysfunction, reduces oxidative stress and exhibits anti-inflammatory effects in ZDF rats, despite persisting hyperlipidemia and hyperinsulinemia. Our preclinical observations provide insights into the mechanisms by which empagliflozin reduces cardiovascular mortality in humans (EMPA-REG trial).
Graphical abstract fx1
Highlights • Hyperglycemia induces vascular complications and cardiovascular disease. • Empagliflozin reduces hyperglycemia and cardiovascular mortality (EMPA-REG trial). • Here, empagliflozin normalized vascular function and oxidative stress in ZDF rats. • Here, empagliflozin reduced AGE/RAGE signaling, inflammation and oxidative stress. • Here, empagliflozin conferred glycemic control, epigenetic and pleiotropic effects.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fac2319499ec3825e6d4ca81494cb48bTest
https://doi.org/10.1016/j.redox.2017.06.009Test