@article{CastanoMartinezSchumacherSchumacheretal.2019, author = {Casta{\~n}o Mart{\´i}nez, Mar{\´i}a Teresa and Schumacher, Fabian and Schumacher, Silke and Kochlik, Bastian Max and Weber, Daniela and Grune, Tilman and Biemann, Ronald and McCann, Adrian and Abraham, Klaus and Weikert, Cornelia and Kleuse, Burkhard and Sch{\"u}rmann, Annette and Laeger, Thomas}, title = {Methionine restriction prevents onset of type 2 diabetes in NZO mice}, series = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology}, volume = {33}, journal = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology}, number = {6}, publisher = {Federation of American Societies for Experimental Biology}, address = {Bethesda}, issn = {0892-6638}, doi = {10.1096/fj.201900150R}, pages = {7092 -- 7102}, year = {2019}, abstract = {Dietary methionine restriction (MR) is well known to reduce body weight by increasing energy expenditure (EE) and insulin sensitivity. An elevated concentration of circulating fibroblast growth factor 21 (FGF21) has been implicated as a potential underlying mechanism. The aims of our study were to test whether dietary MR in the context of a high-fat regimen protects against type 2 diabetes in mice and to investigate whether vegan and vegetarian diets, which have naturally low methionine levels, modulate circulating FGF21 in humans. New Zealand obese (NZO) mice, a model for polygenic obesity and type 2 diabetes, were placed on isocaloric high-fat diets (protein, 16 kcal\%; carbohydrate, 52 kcal\%; fat, 32 kcal\%) that provided methionine at control (Con; 0.86\% methionine) or low levels (0.17\%) for 9 wk. Markers of glucose homeostasis and insulin sensitivity were analyzed. Among humans, low methionine intake and circulating FGF21 levels were investigated by comparing a vegan and a vegetarian diet to an omnivore diet and evaluating the effect of a short-term vegetarian diet on FGF21 induction. In comparison with the Con group, MR led to elevated plasma FGF21 levels and prevented the onset of hyperglycemia in NZO mice. MR-fed mice exhibited increased insulin sensitivity, higher plasma adiponectin levels, increased EE, and up-regulated expression of thermogenic genes in subcutaneous white adipose tissue. Food intake and fat mass did not change. Plasma FGF21 levels were markedly higher in vegan humans compared with omnivores, and circulating FGF21 levels increased significantly in omnivores after 4 d on a vegetarian diet. These data suggest that MR induces FGF21 and protects NZO mice from high-fat diet-induced glucose intolerance and type 2 diabetes. The normoglycemic phenotype in vegans and vegetarians may be caused by induced FGF21. MR akin to vegan and vegetarian diets in humans may offer metabolic benefits via increased circulating levels of FGF21 and merits further investigation.-Castano-Martinez, T., Schumacher, F., Schumacher, S., Kochlik, B., Weber, D., Grune, T., Biemann, R., McCann, A., Abraham, K., Weikert, C., Kleuser, B., Schurmann, A., Laeger, T. Methionine restriction prevents onset of type 2 diabetes in NZO mice.}, language = {en} } @misc{ZimmermannHornConradKampeetal.2020, author = {Zimmermann, Matthias and Horn-Conrad, Antje and Kampe, Heike and Scholz, Jana and Engel, Silke and Eckardt, Barbara and Krafzik, Carolin and Schneider, Simon and Schumacher, Juliane}, title = {Portal Wissen = Energie}, number = {01/2020}, organization = {Universit{\"a}t Potsdam, Referat f{\"u}r Presse- und {\"O}ffentlichkeitsarbeit}, issn = {2194-4237}, doi = {10.25932/publishup-44252}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-442521}, pages = {98}, year = {2020}, abstract = {Energie hat etwas. Nat{\"u}rlich - so die n{\"u}chterne Definition in jedem Sch{\"u}lerlexikon - „die F{\"a}higkeit, mechanische Arbeit zu verrichten, W{\"a}rme abzugeben oder Licht auszustrahlen". Auf diese Weise begleitet sie uns, oft unerkannt, den lieben langen Tag: Aus dem Bett wuchten, die Heizung aufdrehen, das Licht anmachen, heiß duschen, anziehen, Kaffee kochen, fr{\"u}hst{\"u}cken - noch bevor wir das Haus verlassen, haben wir reichlich Energie freigesetzt, umgewandelt, zugef{\"u}hrt und getankt. Und dabei haben wir noch nicht einmal selbst gearbeitet, jedenfalls im herk{\"o}mmlichen Sinn. Aber Energie ist nicht nur eine physikalische Gr{\"o}ße, die aufgrund ihrer Allgegenwart in jeder naturwissenschaftlichen Disziplin - wie Biologie und Chemie, aber auch so ziemlich alle technischen Felder - eine zentrale Rolle spielt. Vielmehr ist sie ebenso nicht wegzudenken, wenn es darum geht, wie wir unsere Welt und unser Wirken in ihr verstehen und beschreiben. Und zwar nicht erst seit heute. Eine Kostprobe gef{\"a}llig? Der griechische Philosoph Aristoteles war der Erste, der von en{\´e}rgeia sprach, f{\"u}r ihn eher unphysikalisch eine lebendige „Wirklichkeit und Wirksamkeit" - das, was das M{\"o}gliche real werden l{\"a}sst. Rund 2100 Jahre sp{\"a}ter erkl{\"a}rte sie der ungekr{\"o}nte K{\"o}nig der deutschen Literatur Johann Wolfgang von Goethe zum humanistischen Wesenskern: „Was k{\"o}nnen wir denn unser Eigenes nennen als die Energie, die Kraft, das Wollen!" Und f{\"u}r seinen Zeitgenossen Wilhelm von Humboldt war „Energie die erste und einzige Tugend des Menschen". Auch wenn die Physik mit ihrem Aufstieg zur Leitwissenschaft im 19. Jahrhundert auch den Energiebegriff zu dominieren begann, blieb dieser doch in vielen Gebieten zu Hause. Grund genug f{\"u}r uns, einmal zu schauen, wo es an der Universit{\"a}t Potsdam energetisch zugeht. Wir wurden in verschiedensten Disziplinen f{\"u}ndig: W{\"a}hrend die iranische Physikerin Safa Shoaee erforscht, wie sich mit organischen Materialien die Solarzellen der Zukunft herstellen lassen, nimmt der schwedische Umweltwissenschaftler Johan Lilliestam die verschiedenen Dimensionen der Energiewende in den Fokus, um zu kl{\"a}ren, wovon ihr Gelingen abh{\"a}ngt. Die Slavistin Susanne Str{\"a}tling wiederum l{\"a}sst auf der Suche nach einer komplexen Begriffsgeschichte s{\"a}mtliche Disziplingrenzen hinter sich und versucht zu ergr{\"u}nden, warum die Energie uns heute mehr denn je elektrisiert. Und dem Physiker Markus G{\"u}hr gelingt es, mithilfe von ultrakurzen Lichtblitzen zu untersuchen, wie sich Molek{\"u}le unter Lichteinfluss ver{\"a}ndern und dabei Energie umwandeln. Freilich haben wir genug Energie, um neben dem Titelthema auch Einblicke in die Vielfalt der Forschung an der Universit{\"a}t Potsdam zusammenzutragen. So erkl{\"a}rt ein Kognitionswissenschaftler, warum unser Hirn Musik und Sprache gleichermaßen nach ihrem Rhythmus verarbeitet, und ein Materialforscher zeigt, wie Bakterien k{\"u}nftig unter richtiger Anleitung biologisch abbaubares Plastik produzieren. Sozialwissenschaftler untersuchen, ob es der Bundeswehr gelingt, echte Gleichstellung f{\"u}r wirklich alle zu schaffen, w{\"a}hrend Umweltwissenschaftler eine Methode entwickeln, bei der sich mithilfe von Teilchen aus dem All die Bodenfeuchte messen l{\"a}sst. Ein Psychologe erforscht den Zusammenhang zwischen Emotionen und Ged{\"a}chtnis und Bildungswissenschaftler bringen eine Studie zu Hate Speech in Schulen auf den Weg. Außerdem stellen wir mit einer Pal{\"a}oklimatologin und einer Astrophysikerin zwei der insgesamt zw{\"o}lf Forschenden des neuen Postdoc-Programms der Universit{\"a}t Potsdam vor. Gin ohne Akohol, Sprachforschung mit Ultraschall, Drohnen im Einsatz der Wissenschaft, Rechtswissenschaft im Dienste der Menschenrechte und vieles mehr finden sich in dieser Ausgabe. Wir haben keine Energien gescheut!}, language = {de} } @article{GereckeEdlichGiulbudagianetal.2017, author = {Gerecke, Christian and Edlich, Alexander and Giulbudagian, Michael and Schumacher, Fabian and Zhang, Nan and Said, Andre and Yealland, Guy and Lohan, Silke B. and Neumann, Falko and Meinke, Martina C. and Ma, Nan and Calderon, Marcelo and Hedtrich, Sarah and Schaefer-Korting, Monika and Kleuser, Burkhard}, title = {Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes}, series = {Nanotoxicology}, volume = {11}, journal = {Nanotoxicology}, publisher = {Routledge, Taylor \& Francis Group}, address = {Abingdon}, issn = {1743-5390}, doi = {10.1080/17435390.2017.1292371}, pages = {267 -- 277}, year = {2017}, abstract = {Novel nanogels that possess the capacity to change their physico-chemical properties in response to external stimuli are promising drug-delivery candidates for the treatment of severe skin diseases. As thermoresponsive nanogels (tNGs) are capable of enhancing penetration through biological barriers such as the stratum corneum and are taken up by keratinocytes of human skin, potential adverse consequences of their exposure must be elucidated. In this study, tNGs were synthesized from dendritic polyglycerol (dPG) and two thermoresponsive polymers. tNG_dPG_tPG are the combination of dPG with poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)) and tNG_dPG_pNIPAM the one with poly(N-isopropylacrylamide) (pNIPAM). Both thermoresponsive nanogels are able to incorporate high amounts of dexamethasone and tacrolimus, drugs used in the treatment of severe skin diseases. Cellular uptake, intracellular localization and the toxicological properties of the tNGs were comprehensively characterized in primary normal human keratinocytes (NHK) and in spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (HaCaT). Laser scanning confocal microscopy revealed fluorescently labeled tNGs entered into the cells and localized predominantly within lysosomal compartments. MTT assay, comet assay and carboxy-H2DCFDA assay, demonstrated neither cytotoxic or genotoxic effects, nor any induction of reactive oxygen species of the tNGs in keratinocytes. In addition, both tNGs were devoid of eye irritation potential as shown by bovine corneal opacity and permeability (BCOP) test and red blood cell (RBC) hemolysis assay. Therefore, our study provides evidence that tNGs are locally well tolerated and underlines their potential for cutaneous drug delivery.}, language = {en} } @article{GiulbudagianHoenzkeBergueiroetal.2018, author = {Giulbudagian, Michael and H{\"o}nzke, Stefan and Bergueiro, Juli{\´a}n and I{\c{s}}{\i}k, Doğu{\c{s}} and Schumacher, Fabian and Saeidpour, Siavash and Lohan, Silke and Meinke, Martina and Teutloff, Christian and Sch{\"a}fer-Korting, Monika and Yealland, Guy and Kleuser, Burkhard and Hedtrich, Sarah and Calder{\´o}n, Marcelo}, title = {Enhanced topical delivery of dexamethasone by beta-cyclodextrin decorated thermoresponsive nanogels}, series = {Nanoscale}, volume = {10}, journal = {Nanoscale}, number = {1}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {2040-3364}, doi = {10.1039/c7nr04480a}, pages = {469 -- 479}, year = {2018}, abstract = {Highly hydrophilic, responsive nanogels are attractive as potential systems for the topical delivery of bioactives encapsulated in their three-dimensional polymeric scaffold. Yet, these drug carrier systems suffer from drawbacks for efficient delivery of hydrophobic drugs. Addressing this, β-cyclodextrin (βCD) could be successfully introduced into the drug carrier systems by exploiting its unique affinity toward dexamethasone (DXM) as well as its role as topical penetration enhancer. The properties of βCD could be combined with those of thermoresponsive nanogels (tNGs) based on dendritic polyglycerol (dPG) as a crosslinker and linear thermoresponsive polyglycerol (tPG) inducing responsiveness to temperature changes. Electron paramagnetic resonance (EPR) studies localized the drug within the hydrophobic cavity of βCD by differences in its mobility and environmental polarity. In fact, the fabricated carriers combining a particulate delivery system with a conventional penetration enhancer, resulted in an efficient delivery of DXM to the epidermis and the dermis of human skin ex vivo (enhancement compared to commercial DXM cream: ∼2.5 fold in epidermis, ∼30 fold in dermis). Furthermore, DXM encapsulated in βCD tNGs applied to skin equivalents downregulated the expression of proinflammatory thymic stromal lymphopoietin (TSLP) and outperformed a commercially available DXM cream.}, language = {en} } @misc{GereckeEdlichGiulbudagianetal.2017, author = {Gerecke, Christian and Edlich, Alexander and Giulbudagian, Michael and Schumacher, Fabian and Zhang, Nan and Said, Andre and Yealland, Guy and Lohan, Silke B. and Neumann, Falko and Meinke, Martina C. and Ma, Nan and Calder{\´o}n, Marcelo and Hedtrich, Sarah and Sch{\"a}fer-Korting, Monika and Kleuser, Burkhard}, title = {Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-395325}, pages = {11}, year = {2017}, abstract = {Novel nanogels that possess the capacity to change their physico-chemical properties in response to external stimuli are promising drug-delivery candidates for the treatment of severe skin diseases. As thermoresponsive nanogels (tNGs) are capable of enhancing penetration through biological barriers such as the stratum corneum and are taken up by keratinocytes of human skin, potential adverse consequences of their exposure must be elucidated. In this study, tNGs were synthesized from dendritic polyglycerol (dPG) and two thermoresponsive polymers. tNG_dPG_tPG are the combination of dPG with poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)) and tNG_dPG_pNIPAM the one with poly(N-isopropylacrylamide) (pNIPAM). Both thermoresponsive nanogels are able to incorporate high amounts of dexamethasone and tacrolimus, drugs used in the treatment of severe skin diseases. Cellular uptake, intracellular localization and the toxicological properties of the tNGs were comprehensively characterized in primary normal human keratinocytes (NHK) and in spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (HaCaT). Laser scanning confocal microscopy revealed fluorescently labeled tNGs entered into the cells and localized predominantly within lysosomal compartments. MTT assay, comet assay and carboxy-H2DCFDA assay, demonstrated neither cytotoxic or genotoxic effects, nor any induction of reactive oxygen species of the tNGs in keratinocytes. In addition, both tNGs were devoid of eye irritation potential as shown by bovine corneal opacity and permeability (BCOP) test and red blood cell (RBC) hemolysis assay. Therefore, our study provides evidence that tNGs are locally well tolerated and underlines their potential for cutaneous drug delivery.}, language = {en} }