@misc{WotingBlaut2016, author = {Woting, Anni and Blaut, Michael}, title = {The intestinal microbiota in metabolic disease}, series = {Nutrients}, journal = {Nutrients}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-407687}, pages = {19}, year = {2016}, abstract = {Gut bacteria exert beneficial and harmful effects in metabolic diseases as deduced from the comparison of germfree and conventional mice and from fecal transplantation studies. Compositional microbial changes in diseased subjects have been linked to adiposity, type 2 diabetes and dyslipidemia. Promotion of an increased expression of intestinal nutrient transporters or a modified lipid and bile acid metabolism by the intestinal microbiota could result in an increased nutrient absorption by the host. The degradation of dietary fiber and the subsequent fermentation of monosaccharides to short-chain fatty acids (SCFA) is one of the most controversially discussed mechanisms of how gut bacteria impact host physiology. Fibers reduce the energy density of the diet, and the resulting SCFA promote intestinal gluconeogenesis, incretin formation and subsequently satiety. However, SCFA also deliver energy to the host and support liponeogenesis. Thus far, there is little knowledge on bacterial species that promote or prevent metabolic disease. Clostridium ramosum and Enterococcus cloacae were demonstrated to promote obesity in gnotobiotic mouse models, whereas bifidobacteria and Akkermansia muciniphila were associated with favorable phenotypes in conventional mice, especially when oligofructose was fed. How diet modulates the gut microbiota towards a beneficial or harmful composition needs further research. Gnotobiotic animals are a valuable tool to elucidate mechanisms underlying diet-host-microbe interactions.}, language = {en} } @article{WolffGastEversetal.2021, author = {Wolff, Martin and Gast, Klaus and Evers, Andreas and Kurz, Michael and Pfeiffer-Marek, Stefania and Sch{\"u}ler, Anja and Seckler, Robert and Thalhammer, Anja}, title = {A Conserved Hydrophobic Moiety and Helix-Helix Interactions Drive the Self-Assembly of the Incretin Analog Exendin-4}, series = {Biomolecules}, volume = {11}, journal = {Biomolecules}, number = {9}, publisher = {MDPI}, address = {Basel}, issn = {2218-273X}, doi = {10.3390/biom11091305}, pages = {20}, year = {2021}, abstract = {Exendin-4 is a pharmaceutical peptide used in the control of insulin secretion. Structural information on exendin-4 and related peptides especially on the level of quaternary structure is scarce. We present the first published association equilibria of exendin-4 directly measured by static and dynamic light scattering. We show that exendin-4 oligomerization is pH dependent and that these oligomers are of low compactness. We relate our experimental results to a structural hypothesis to describe molecular details of exendin-4 oligomers. Discussion of the validity of this hypothesis is based on NMR, circular dichroism and fluorescence spectroscopy, and light scattering data on exendin-4 and a set of exendin-4 derived peptides. The essential forces driving oligomerization of exendin-4 are helix-helix interactions and interactions of a conserved hydrophobic moiety. Our structural hypothesis suggests that key interactions of exendin-4 monomers in the experimentally supported trimer take place between a defined helical segment and a hydrophobic triangle constituted by the Phe22 residues of the three monomeric subunits. Our data rationalize that Val19 might function as an anchor in the N-terminus of the interacting helix-region and that Trp25 is partially shielded in the oligomer by C-terminal amino acids of the same monomer. Our structural hypothesis suggests that the Trp25 residues do not interact with each other, but with C-terminal Pro residues of their own monomers.}, language = {en} } @misc{WolffGastEversetal.2021, author = {Wolff, Martin and Gast, Klaus and Evers, Andreas and Kurz, Michael and Pfeiffer-Marek, Stefania and Sch{\"u}ler, Anja and Seckler, Robert and Thalhammer, Anja}, title = {A Conserved Hydrophobic Moiety and Helix-Helix Interactions Drive the Self-Assembly of the Incretin Analog Exendin-4}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {9}, issn = {1866-8372}, doi = {10.25932/publishup-52208}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-522081}, pages = {22}, year = {2021}, abstract = {Exendin-4 is a pharmaceutical peptide used in the control of insulin secretion. Structural information on exendin-4 and related peptides especially on the level of quaternary structure is scarce. We present the first published association equilibria of exendin-4 directly measured by static and dynamic light scattering. We show that exendin-4 oligomerization is pH dependent and that these oligomers are of low compactness. We relate our experimental results to a structural hypothesis to describe molecular details of exendin-4 oligomers. Discussion of the validity of this hypothesis is based on NMR, circular dichroism and fluorescence spectroscopy, and light scattering data on exendin-4 and a set of exendin-4 derived peptides. The essential forces driving oligomerization of exendin-4 are helix-helix interactions and interactions of a conserved hydrophobic moiety. Our structural hypothesis suggests that key interactions of exendin-4 monomers in the experimentally supported trimer take place between a defined helical segment and a hydrophobic triangle constituted by the Phe22 residues of the three monomeric subunits. Our data rationalize that Val19 might function as an anchor in the N-terminus of the interacting helix-region and that Trp25 is partially shielded in the oligomer by C-terminal amino acids of the same monomer. Our structural hypothesis suggests that the Trp25 residues do not interact with each other, but with C-terminal Pro residues of their own monomers.}, language = {en} } @misc{vonWebskyReichetzederHocher2014, author = {von Websky, Karoline and Reichetzeder, Christoph and Hocher, Berthold}, title = {Physiology and pathophysiology of incretins in the kidney}, series = {Current opinion in nephrology and hypertension : reviews of all advances, evaluations of key references, comprehensive listing of papers}, volume = {23}, journal = {Current opinion in nephrology and hypertension : reviews of all advances, evaluations of key references, comprehensive listing of papers}, number = {1}, publisher = {Lippincott Williams \& Wilkins}, address = {Philadelphia}, issn = {1062-4821}, doi = {10.1097/01.mnh.0000437542.77175.a0}, pages = {54 -- 60}, year = {2014}, abstract = {Purpose of reviewIncretin-based therapy with glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors is considered a promising therapeutic option for type 2 diabetes mellitus. Cumulative evidence, mainly from preclinical animal studies, reveals that incretin-based therapies also may elicit beneficial effects on kidney function. This review gives an overview of the physiology, pathophysiology, and pharmacology of the renal incretin system.Recent findingsActivation of GLP-1R in the kidney leads to diuretic and natriuretic effects, possibly through direct actions on renal tubular cells and sodium transporters. Moreover, there is evidence that incretin-based therapy reduces albuminuria, glomerulosclerosis, oxidative stress, and fibrosis in the kidney, partially through GLP-1R-independent pathways. Molecular mechanisms by which incretins exert their renal effects are understood incompletely, thus further studies are needed.SummaryThe GLP-1R and DPP-4 are expressed in the kidney in various species. The kidney plays an important role in the excretion of incretin metabolites and most GLP-1R agonists and DPP-4 inhibitors, thus special attention is required when applying incretin-based therapy in renal impairment. Preclinical observations suggest direct renoprotective effects of incretin-based therapies in the setting of hypertension and other disorders of sodium retention, as well as in diabetic and nondiabetic nephropathy. Clinical studies are needed in order to confirm translational relevance from preclinical findings for treatment options of renal diseases.}, language = {en} } @article{OlamoyegunRaimiAlaetal.2020, author = {Olamoyegun, Michael Adeyemi and Raimi, Taiwo Hassan and Ala, Oluwabukola Ayodele and Fadare, Joseph Olusesan}, title = {Mobile phone ownership and willingness to receive mHealth services among patients with diabetes mellitus in South-West, Nigeria}, series = {Pan African medical journal : PAMJ}, volume = {37}, journal = {Pan African medical journal : PAMJ}, publisher = {African Field Epidemiology Network (AFENET)}, address = {Kampala, Uganda}, issn = {1937-8688}, doi = {10.11604/pamj.2020.37.29.25174}, pages = {13}, year = {2020}, abstract = {Introduction: mobile phone technology is increasingly used to overcome traditional barriers to limiting access to diabetes care. This study evaluated mobile phone ownership and willingness to receive and pay for mobile phone-based diabetic services among people with diabetes in South-West, Nigeria. Methods: two hundred and fifty nine patients with diabetes were consecutively recruited from three tertiary health institutions in South-West, Nigeria. Questionnaire was used to evaluate mobile phone ownership, willingness to receive and pay for mobile phone-based diabetic health care services via voice call and text messaging. Results: 97.3\% owned a mobile phone, with 38.9\% and 61.1\% owning smartphone and basic phone respectively. Males were significantly more willing to receive mobile-phone-based health services than females (81.1\% vs 68.1\%, p=0.025), likewise married compared to unmarried [77.4\% vs 57.1\%, p=0.0361. Voice calls (41.3\%) and text messages (32.4\%), were the most preferred modes of receiving diabetes-related health education with social media (3.1\%) and email (1.5\%) least. Almost three-quarter of participants (72.6\%) who owned mobile phone, were willing to receive mobile phone-based diabetes health services. The educational status of patients (adjusted OR [AORJ: 1.7(95\% CI: 1.6 to 2.11), glucometers possession (ACM: 2.0 [95\% CI: 1.9 to 2.1) and type of mobile phone owned (AOR: 2.9 [95\% CI: 2.8 to 5.0]) were significantly associated with the willingness to receive mobile phone-based diabetic services. Conclusion: the majority of study participants owned mobile phones and would be willing to receive and pay for diabetes-related healthcare delivery services provided the cost is minimal and affordable.}, language = {en} } @article{MoserMaderTschakertetal.2016, author = {Moser, Othmar and Mader, Julia K. and Tschakert, Gerhard and Mueller, Alexander and Groeschl, Werner and Pieber, Thomas R. and Koehler, Gerd and Messerschmidt, Janin and Hofmann, Peter}, title = {Accuracy of Continuous Glucose Monitoring (CGM) during Continuous and High-Intensity Interval Exercise in Patients with Type 1 Diabetes Mellitus}, series = {Nutrients}, volume = {8}, journal = {Nutrients}, publisher = {MDPI}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu8080489}, pages = {15}, year = {2016}, abstract = {Continuous exercise (CON) and high-intensity interval exercise (HIIE) can be safely performed with type 1 diabetes mellitus (T1DM). Additionally, continuous glucose monitoring (CGM) systems may serve as a tool to reduce the risk of exercise-induced hypoglycemia. It is unclear if CGM is accurate during CON and HIIE at different mean workloads. Seven T1DM patients performed CON and HIIE at 5\% below (L) and above (M) the first lactate turn point (LTP1), and 5\% below the second lactate turn point (LTP2) (H) on a cycle ergometer. Glucose was measured via CGM and in capillary blood (BG). Differences were found in comparison of CGM vs. BG in three out of the six tests (p < 0.05). In CON, bias and levels of agreement for L, M, and H were found at: 0.85 (-3.44, 5.15) mmol.L-1, -0.45 (-3.95, 3.05) mmol.L-1, -0.31 (-8.83, 8.20) mmol.L-1 and at 1.17 (-2.06, 4.40) mmol.L-1, 0.11 (-5.79, 6.01) mmol.L-1, 1.48 (-2.60, 5.57) mmol.L-1 in HIIE for the same intensities. Clinically-acceptable results (except for CON H) were found. CGM estimated BG to be clinically acceptable, except for CON H. Additionally, using CGM may increase avoidance of exercise-induced hypoglycemia, but usual BG control should be performed during intense exercise.}, language = {en} } @misc{MoserMaderTschakertetal.2017, author = {Moser, Othmar and Mader, Julia K. and Tschakert, Gerhard and Mueller, Alexander and Groeschl, Werner and Pieber, Thomas R. and Koehler, Gerd and Messerschmidt, Janin and Hofmann, Peter}, title = {Accuracy of Continuous Glucose Monitoring (CGM) during continuous and high-intensity interval exercise in patients with Type 1 Diabetes Mellitus}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-400470}, pages = {15}, year = {2017}, abstract = {Continuous exercise (CON) and high-intensity interval exercise (HIIE) can be safely performed with type 1 diabetes mellitus (T1DM). Additionally, continuous glucose monitoring (CGM) systems may serve as a tool to reduce the risk of exercise-induced hypoglycemia. It is unclear if CGM is accurate during CON and HIIE at different mean workloads. Seven T1DM patients performed CON and HIIE at 5\% below (L) and above (M) the first lactate turn point (LTP1), and 5\% below the second lactate turn point (LTP2) (H) on a cycle ergometer. Glucose was measured via CGM and in capillary blood (BG). Differences were found in comparison of CGM vs. BG in three out of the six tests (p < 0.05). In CON, bias and levels of agreement for L, M, and H were found at: 0.85 (-3.44, 5.15) mmol·L-1, -0.45 (-3.95, 3.05) mmol·L-1, -0.31 (-8.83, 8.20) mmol·L-1 and at 1.17 (-2.06, 4.40) mmol·L-1, 0.11 (-5.79, 6.01) mmol·L-1, 1.48 (-2.60, 5.57) mmol·L-1 in HIIE for the same intensities. Clinically-acceptable results (except for CON H) were found. CGM estimated BG to be clinically acceptable, except for CON H. Additionally, using CGM may increase avoidance of exercise-induced hypoglycemia, but usual BG control should be performed during intense exercise.}, language = {en} } @phdthesis{Kluth2012, author = {Kluth, Oliver}, title = {Einfluss von Glucolipotoxizit{\"a}t auf die Funktion der β-Zellen diabetessuszeptibler und -resistenter Mausst{\"a}mme}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-61961}, school = {Universit{\"a}t Potsdam}, year = {2012}, abstract = {Ziel der vorliegenden Arbeit war es, die Auswirkungen von Glucose- und Lipidtoxizit{\"a}t auf die Funktion der β-Zellen von Langerhans-Inseln in einem diabetesresistenten (B6.V-Lepob/ob, ob/ob) sowie diabetessuszeptiblen (New Zealand Obese, NZO) Mausmodell zu untersuchen. Es sollten molekulare Mechanismen identifiziert werden, die zum Untergang der β-Zellen in der NZO-Maus f{\"u}hren bzw. zum Schutz der β-Zellen der ob/ob-Maus beitragen. Zun{\"a}chst wurde durch ein geeignetes di{\"a}tetisches Regime in beiden Modellen durch kohlenhydratrestriktive Ern{\"a}hrung eine Adipositas(Lipidtoxizit{\"a}t) induziert und anschließend durch F{\"u}tterung einer kohlenhydrathaltigen Di{\"a}t ein Zustand von Glucolipotoxizit{\"a}t erzeugt. Dieses Vorgehen erlaubte es, in der NZO-Maus in einem kurzen Zeitfenster eine Hyperglyk{\"a}mie sowie einen β-Zelluntergang durch Apoptose auszul{\"o}sen. Im Vergleich dazu blieben ob/ob-M{\"a}use l{\"a}ngerfristig normoglyk{\"a}misch und wiesen keinen β-Zelluntergang auf. Die Ursache f{\"u}r den β-Zellverlust war die Inaktivierung des Insulin/IGF-1-Rezeptor-Signalwegs, wie durch Abnahme von phospho-AKT, phospho-FoxO1 sowie des β-zellspezifischen Transkriptionsfaktors PDX1 gezeigt wurde. Mit Ausnahme des Effekts einer Dephosphorylierung von FoxO1, konnten ob/ob-M{\"a}use diesen Signalweg aufrechterhalten und dadurch einen Verlust von β-Zellen abwenden. Die glucolipotoxischen Effekte wurden in vitro an isolierten Inseln beider St{\"a}mme und der β-Zelllinie MIN6 best{\"a}tigt und zeigten, dass ausschließlich die Kombination hoher Glucose und Palmitatkonzentrationen (Glucolipotoxizit{\"a}t) negative Auswirkungen auf die NZO-Inseln und MIN6-Zellen hatte, w{\"a}hrend ob/ob-Inseln davor gesch{\"u}tzt blieben. Die Untersuchung isolierter Inseln ergab, dass beide St{\"a}mme unter glucolipotoxischen Bedingungen keine Steigerung der Insulinexpression aufweisen und sich bez{\"u}glich ihrer Glucose-stimulierten Insulinsekretion nicht unterscheiden. Mit Hilfe von Microarray- sowie immunhistologischen Untersuchungen wurde gezeigt, dass ausschließlich ob/ob-M{\"a}use nach Kohlenhydratf{\"u}tterung eine kompensatorische transiente Induktion der β-Zellproliferation aufwiesen, die in einer nahezu Verdreifachung der Inselmasse nach 32 Tagen m{\"u}ndete. Die hier erzielten Ergebnisse lassen die Schlussfolgerung zu, dass der β-Zelluntergang der NZO-Maus auf eine Beeintr{\"a}chtigung des Insulin/IGF-1-Rezeptor-Signalwegs sowie auf die Unf{\"a}higkeit zur β- Zellproliferation zur{\"u}ckgef{\"u}hrt werden kann. Umgekehrt erm{\"o}glichen der Erhalt des Insulin/IGF-1-Rezeptor-Signalwegs und die Induktion der β-Zellproliferation in der ob/ob-Maus den Schutz vor einer Hyperglyk{\"a}mie und einem Diabetes.}, language = {de} } @article{JonasKluthHelmsetal.2022, author = {Jonas, Wenke and Kluth, Oliver and Helms, Anett and Voss, Sarah and Jahnert, Markus and Gottmann, Pascal and Speckmann, Thilo and Knebel, Birgit and Chadt, Alexandra and Al-Hasani, Hadi and Sch{\"u}rmann, Annette and Vogel, Heike}, title = {Identification of novel genes involved in hyperglycemia in mice}, series = {International journal of molecular sciences}, volume = {23}, journal = {International journal of molecular sciences}, number = {6}, publisher = {MDPI}, address = {Basel}, issn = {1661-6596}, doi = {10.3390/ijms23063205}, pages = {13}, year = {2022}, abstract = {Current attempts to prevent and manage type 2 diabetes have been moderately effective, and a better understanding of the molecular roots of this complex disease is important to develop more successful and precise treatment options. Recently, we initiated the collective diabetes cross, where four mouse inbred strains differing in their diabetes susceptibility were crossed with the obese and diabetes-prone NZO strain and identified the quantitative trait loci (QTL) Nidd13/NZO, a genomic region on chromosome 13 that correlates with hyperglycemia in NZO allele carriers compared to B6 controls. Subsequent analysis of the critical region, harboring 644 genes, included expression studies in pancreatic islets of congenic Nidd13/NZO mice, integration of single-cell data from parental NZO and B6 islets as well as haplotype analysis. Finally, of the five genes (Acot12, S100z, Ankrd55, Rnf180, and Iqgap2) within the polymorphic haplotype block that are differently expressed in islets of B6 compared to NZO mice, we identified the calcium-binding protein S100z gene to affect islet cell proliferation as well as apoptosis when overexpressed in MINE cells. In summary, we define S100z as the most striking gene to be causal for the diabetes QTL Nidd13/NZO by affecting beta-cell proliferation and apoptosis. Thus, S100z is an entirely novel diabetes gene regulating islet cell function.}, language = {en} } @article{JannaschNickelBergmannetal.2022, author = {Jannasch, Franziska and Nickel, Daniela V. and Bergmann, Manuela M. and Schulze, Matthias Bernd}, title = {A new evidence-based diet score to capture associations of food consumption and chronic disease risk}, series = {Nutrients / Molecular Diversity Preservation International (MDPI)}, volume = {14}, journal = {Nutrients / Molecular Diversity Preservation International (MDPI)}, number = {11}, publisher = {MDPI}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu14112359}, pages = {16}, year = {2022}, abstract = {Previously, the attempt to compile German dietary guidelines into a diet score was predominantly not successful with regards to preventing chronic diseases in the EPIC-Potsdam study. Current guidelines were supplemented by the latest evidence from systematic reviews and expert papers published between 2010 and 2020 on the prevention potential of food groups on chronic diseases such as type 2 diabetes, cardiovascular diseases and cancer. A diet score was developed by scoring the food groups according to a recommended low, moderate or high intake. The relative validity and reliability of the diet score, assessed by a food frequency questionnaire, was investigated. The consideration of current evidence resulted in 10 key food groups being preventive of the chronic diseases of interest. They served as components in the diet score and were scored from 0 to 1 point, depending on their recommended intake, resulting in a maximum of 10 points. Both the reliability (r = 0.53) and relative validity (r = 0.43) were deemed sufficient to consider the diet score as a stable construct in future investigations. This new diet score can be a promising tool to investigate dietary intake in etiological research by concentrating on 10 key dietary determinants with evidence-based prevention potential for chronic diseases.}, language = {en} }