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Your search keyword '"Marquard, Jan"' showing total 2 results
Start Over Author "Marquard, Jan" Journal nature medicine
2 results on '"Marquard, Jan"'

1. Characterization of pancreatic NMDA receptors as possible drug targets for diabetes treatment

Author

Marquard, Jan, Otter, Silke, Welters, Alena, Stirban, Alin, Fischer, Annelie, Eglinger, Jan, Herebian, Diran, Kletke, Olaf, Klemen, Masa Skelin, Stozer, Andraz, Wnendt, Stephan, Piemonti, Lorenzo, Kohler, Martin, Ferrer, Jorge, Thorens, Bernard, Schliess, Freimut, Rupnik, Marjan Slak, Heise, Tim, Berggren, Per-Olof, Klocker, Nikolaj, Meissner, Thomas, Mayatepek, Ertan, Eberhard, Daniel, Kragl, Martin, and Lammert, Eckhard

Subjects
Medical research, Medicine, Experimental, Methyl aspartate -- Research, Diabetes therapy -- Research, Diabetes -- Drug therapy, Drug targeting -- Research, Type 2 diabetes -- Research, Biological sciences, Health
Abstract

In the nervous system, NMDA receptors (NMDARs) participate in neurotransmission and modulate the viability of neurons. In contrast, little is known about the role of NMDARs in pancreatic islets and the insulin-secreting beta cells whose functional impairment contributes to diabetes mellitus. Here we found that inhibition of NMDARs in mouse and human islets enhanced their glucose-stimulated insulin secretion (GSIS) and survival of islet cells. Further, NMDAR inhibition prolonged the amount of time that glucose-stimulated beta cells spent in a depolarized state with high cytosolic [Ca.sup.2+] concentrations. We also noticed that, in vivo, the NMDAR antagonist dextromethorphan (DXM) enhanced glucose tolerance in mice, and that in vitro dextrorphan, the main metabolite of DXM, amplified the stimulatory effect of exendin-4 on GSIS. In a mouse model of type 2 diabetes mellitus (T2DM), long-term treatment with DXM improved islet insulin content, islet cell mass and blood glucose control. Further, in a small clinical trial we found that individuals with T2DM treated with DXM showed enhanced serum insulin concentrations and glucose tolerance. Our data highlight the possibility that antagonists of NMDARs may provide a useful adjunct treatment for diabetes., Type 2 diabetes mellitus (T2DM) is the most common metabolic disease worldwide, affecting more than 350 million people, and both its incidence and prevalence have been increasing globally (1). Peripheral [...]

Published
2015
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2. Characterization of pancreatic NMDA receptors as possible drug targets for diabetes treatment

Author

Jan Eglinger, Maša Skelin Klemen, Olaf Kletke, Eckhard Lammert, Daniel Eberhard, Alena Welters, Silke Otter, Martin Köhler, Stephan Wnendt, Nikolaj Klöcker, Annelie Fischer, Jorge Ferrer, Tim Heise, Diran Herebian, Ertan Mayatepek, Thomas Meissner, Lorenzo Piemonti, Andraž Stožer, Freimut Schliess, Martin Kragl, Bernard Thorens, Per Olof Berggren, Marjan Slak Rupnik, Alin Stirban, Jan Marquard, Marquard, Jan, Otter, Silke, Welters, Alena, Stirban, Alin, Fischer, Annelie, Eglinger, Jan, Herebian, Diran, Kletke, Olaf, Klemen, MaÅ¡a Skelin, Stoå¾er, Andraå, Wnendt, Stephan, Piemonti, Lorenzo, Kã¶hler, Martin, Ferrer, Jorge, Thorens, Bernard, Schliess, Freimut, Rupnik, Marjan Slak, Heise, Tim, Berggren, Per Olof, Klã¶cker, Nikolaj, Meissner, Thoma, Mayatepek, Ertan, Eberhard, Daniel, Kragl, Martin, Lammert, Eckhard, and Pathology/molecular and cellular medicine

Subjects
Male, endocrine system diseases, medicine.medical_treatment, Dextromethorphan, Mice, Dextrorphan, Insulin-Secreting Cells, Pancrea, Insulin, Mice, Knockout, Glucose tolerance test, geography.geographical_feature_category, medicine.diagnostic_test, Research Support, Non-U.S. Gov't, Medicine (all), General Medicine, Middle Aged, Islet, 3. Good health, medicine.anatomical_structure, Peptide, Female, medicine.drug, Human, Adult, endocrine system, medicine.medical_specialty, Cell Survival, Nerve Tissue Proteins, Receptors, N-Methyl-D-Aspartate, General Biochemistry, Genetics and Molecular Biology, Cell Line, Islets of Langerhans, Research Support, N.I.H., Extramural, Internal medicine, Diabetes mellitus, Journal Article, medicine, Animals, Humans, Pancreas, geography, Biochemistry, Genetics and Molecular Biology (all), business.industry, Animal, Venoms, Pancreatic islets, Type 2 Diabetes Mellitus, Islets of Langerhan, Glucose Tolerance Test, medicine.disease, Venom, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, Glucose, nervous system, Diabetes Mellitus, Type 2, Insulin-Secreting Cell, Drug Design, Nerve Tissue Protein, Exenatide, Calcium, business, Peptides
Abstract

In the nervous system, NMDA receptors (NMDARs) participate in neurotransmission and modulate the viability of neurons. In contrast, little is known about the role of NMDARs in pancreatic islets and the insulin-secreting beta cells whose functional impairment contributes to diabetes mellitus. Here we found that inhibition of NMDARs in mouse and human islets enhanced their glucose-stimulated insulin secretion (GSIS) and survival of islet cells. Further, NMDAR inhibition prolonged the amount of time that glucose-stimulated beta cells spent in a depolarized state with high cytosolic Ca(2+) concentrations. We also noticed that, in vivo, the NMDAR antagonist dextromethorphan (DXM) enhanced glucose tolerance in mice, and that in vitro dextrorphan, the main metabolite of DXM, amplified the stimulatory effect of exendin-4 on GSIS. In a mouse model of type 2 diabetes mellitus (T2DM), long-term treatment with DXM improved islet insulin content, islet cell mass and blood glucose control. Further, in a small clinical trial we found that individuals with T2DM treated with DXM showed enhanced serum insulin concentrations and glucose tolerance. Our data highlight the possibility that antagonists of NMDARs may provide a useful adjunct treatment for diabetes.

Published
2014

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