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  1. Article ; Online: Real-World Use of Once-Weekly Semaglutide in Type 2 Diabetes: Results from SemaglUtide Real-world Evidence (SURE) Germany.

    Menzen, Markus / Berentzen, Tina Landsvig / Catarig, Andrei-Mircea / Pieperhoff, Sebastian / Simon, Jörg / Jacob, Stephan

    Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association

    2023  Volume 131, Issue 4, Page(s) 205–215

    Abstract: Context: Efficacy and safety of once-weekly semaglutide in type 2 diabetes were established in the phase 3 SUSTAIN trials, which included patients across the continuum of type 2 diabetes care. It is useful to complement these findings with real-world ... ...

    Abstract Context: Efficacy and safety of once-weekly semaglutide in type 2 diabetes were established in the phase 3 SUSTAIN trials, which included patients across the continuum of type 2 diabetes care. It is useful to complement these findings with real-world evidence.
    Objective: SURE Germany evaluated once-weekly semaglutide in a real-world type 2 diabetes patient population.
    Design/setting: The prospective observational study was conducted at 93 clinical practices in adults with+≥ 1 documented glycated haemoglobin value ≤12 weeks before initiation of semaglutide.
    Intervention: Once-weekly semaglutide was prescribed at the physicians' discretion.
    Main outcomes: The primary endpoint was change in glycated haemoglobin from baseline to end-of-study (~30 weeks). Secondary endpoints included changes in body weight and patient-reported outcomes. All adverse events were systematically collected and reported, including patient-reported documented and/or severe hypoglycaemia.
    Results: Of 779 patients in the full analysis set, 669 (85.9%) completed the study on treatment with semaglutide, comprising the effectiveness analysis set. In this data set, estimated mean changes in glycated haemoglobin and body weight from baseline to end-of-study were -1.0%point (-10.9 mmol/mol;
    Conclusions: In a real-world population in Germany, patients with type 2 diabetes treated with once-weekly semaglutide experienced clinically significant improvements in glycaemic control and body weight. These results support the use of once-weekly semaglutide in routine clinical practice in adult patients with type 2 diabetes in Germany.
    MeSH term(s) Adult ; Humans ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/epidemiology ; Hypoglycemic Agents/adverse effects ; Glycated Hemoglobin ; Body Weight
    Chemical Substances Hypoglycemic Agents ; semaglutide (53AXN4NNHX) ; Glycated Hemoglobin
    Language English
    Publishing date 2023-01-04
    Publishing country Germany
    Document type Observational Study ; Journal Article
    ZDB-ID 1225416-2
    ISSN 1439-3646 ; 0947-7349
    ISSN (online) 1439-3646
    ISSN 0947-7349
    DOI 10.1055/a-2007-2061
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  2. Article ; Online: Gene Mutations Resulting in the Development of ARVC/D Could Affect Cells of the Cardiac Conduction System.

    Pieperhoff, Sebastian

    Frontiers in physiology

    2012  Volume 3, Page(s) 22

    Abstract: In contrast to epithelial cells, cardiomyocytes are connected by complex hybrid-type adhering junctions, termed composite junctions (areae compositae). Composite junctions are found to be composed of typical desmosomal as well as adherens junction ... ...

    Abstract In contrast to epithelial cells, cardiomyocytes are connected by complex hybrid-type adhering junctions, termed composite junctions (areae compositae). Composite junctions are found to be composed of typical desmosomal as well as adherens junction proteins. Therefore, in adult mammalian cardiomyocytes desmosomal proteins are not restricted to the relatively small desmosomes but are indirectly involved in anchoring the myofibrillar actin filaments. Subsequent investigations revealed that the formation of composite junctions is a rather late event during mammalian heart development and vertebrate heart evolution. Nascent, more round shaped cardiomyocytes of early developmental stages are connected by desmosomes and separate adherens junctions quite similar to cells of epithelial origin. During progression of development both types of adhering junctions seem to gradually fuse at the two poles of the mature mammalian cardiomyocytes to establish the hybrid-type composite junctions. Recently, we demonstrated that the specialized cardiomyocytes of the cardiac conduction system exhibit high amounts of desmosomes, not fully established composite junctions and adherens junctions. This underlines the fact that cells of the cardiac conduction system are known to resemble cardiomyocytes in their nascent state and do not undergo working myocardial differentiation. However, the astonishing high amount of desmosomal protein containing adhering junctions connecting, e.g., Purkinje fibers raises the possibility that pacemaker and conductive tissue may be affected by desmosomal gene mutations in ARVC/D patients.
    Language English
    Publishing date 2012-02-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X ; 1664-042X
    ISSN (online) 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2012.00022
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  3. Article: [No title information]

    Menzen, Markus / Berentzen, Tina Landsvig / Catarig, Andrei-Mircea / Pieperhoff, Sebastian / Simon, Jörg / Jacob, Stephan

    Experimental and Clinical Endocrinology & Diabetes

    2023  Volume 131, Issue 04, Page(s) 205–215

    Abstract: Context: Efficacy and safety of once-weekly semaglutide in type 2 diabetes were established in the phase 3 SUSTAIN trials, which included patients across the continuum of type 2 diabetes care. It is useful to ... ...

    Abstract Context: Efficacy and safety of once-weekly semaglutide in type 2 diabetes were established in the phase 3 SUSTAIN trials, which included patients across the continuum of type 2 diabetes care. It is useful to complement these findings with real-world evidence.
    Objective: SURE Germany evaluated once-weekly semaglutide in a real-world type 2 diabetes patient population.
    Design/setting: The prospective observational study was conducted at 93 clinical practices in adults with+≥ 1 documented glycated haemoglobin value ≤12 weeks before initiation of semaglutide.
    Intervention: Once-weekly semaglutide was prescribed at the physicians’ discretion.
    Main outcomes: The primary endpoint was change in glycated haemoglobin from baseline to end-of-study (~30 weeks). Secondary endpoints included changes in body weight and patient-reported outcomes. All adverse events were systematically collected and reported, including patient-reported documented and/or severe hypoglycaemia.
    Results: Of 779 patients in the full analysis set, 669 (85.9%) completed the study on treatment with semaglutide, comprising the effectiveness analysis set. In this data set, estimated mean changes in glycated haemoglobin and body weight from baseline to end-of-study were –1.0%point (–10.9 mmol/mol; P <0.0001) and –4.5 kg (–4.2%; P <0.0001). Sensitivity analyses supported the primary analysis. Improvements were observed in other secondary endpoints, including patient-reported outcomes. No new safety concerns were identified.
    Conclusions: In a real-world population in Germany, patients with type 2 diabetes treated with once-weekly semaglutide experienced clinically significant improvements in glycaemic control and body weight. These results support the use of once-weekly semaglutide in routine clinical practice in adult patients with type 2 diabetes in Germany.
    Keywords blood pressure ; clinical practice ; patient-reported outcomes ; real-world evidence ; glucagon-like peptide-1 receptor agonist
    Language English
    Publishing date 2023-01-04
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 1225416-2
    ISSN 1439-3646 ; 0947-7349
    ISSN (online) 1439-3646
    ISSN 0947-7349
    DOI 10.1055/a-2007-2061
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  4. Article ; Conference proceedings: Real-world use of once-weekly semaglutide in type 2 diabetes: results from SURE Germany

    Menzen, Markus / Berentzen, Tina Landsvig / Catarig, Andrei-Mircea / Pieperhoff, Sebastian / Simon, Jörg / Jacob, Stephan

    Diabetologie und Stoffwechsel

    2022  Volume 17, Issue S 01

    Event/congress Diabetes Kongress 2022 - 56. Jahrestagung der DDG, CityCube Berlin, 2022-05-25
    Language English
    Publishing date 2022-05-01
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article ; Conference proceedings
    ZDB-ID 2222993-0
    ISSN 1861-9010 ; 1861-9002
    ISSN (online) 1861-9010
    ISSN 1861-9002
    DOI 10.1055/s-0042-1746340
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  5. Article: Identification of Phonology-Related Genes and Functional Characterization of Broca's and Wernicke's Regions in Language and Learning Disorders.

    Unger, Nina / Heim, Stefan / Hilger, Dominique I / Bludau, Sebastian / Pieperhoff, Peter / Cichon, Sven / Amunts, Katrin / Mühleisen, Thomas W

    Frontiers in neuroscience

    2021  Volume 15, Page(s) 680762

    Abstract: Impaired phonological processing is a leading symptom of multifactorial language and learning disorders suggesting a common biological basis. Here we evaluated studies of dyslexia, dyscalculia, specific language impairment (SLI), and the logopenic ... ...

    Abstract Impaired phonological processing is a leading symptom of multifactorial language and learning disorders suggesting a common biological basis. Here we evaluated studies of dyslexia, dyscalculia, specific language impairment (SLI), and the logopenic variant of primary progressive aphasia (lvPPA) seeking for shared risk genes in Broca's and Wernicke's regions, being key for phonological processing within the complex language network. The identified "phonology-related genes" from literature were functionally characterized using Atlas-based expression mapping (JuGEx) and gene set enrichment. Out of 643 publications from the last decade until now, we extracted 21 candidate genes of which 13 overlapped with dyslexia and SLI, six with dyslexia and dyscalculia, and two with dyslexia, dyscalculia, and SLI. No overlap was observed between the childhood disorders and the late-onset lvPPA often showing symptoms of learning disorders earlier in life. Multiple genes were enriched in Gene Ontology terms of the topics learning (
    Language English
    Publishing date 2021-09-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2021.680762
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  6. Article ; Online: Gene mutations resulting in the development of ARVC/D could affect cardiac pacemaker and conductive tissue

    SebastianPieperhoff

    Frontiers in Physiology, Vol

    2012  Volume 3

    Abstract: In contrast to epithelial cells, cardiomyocytes are connected by complex hybrid-type adhering junctions, termed composite junctions (areae compositae). Composite junctions are found to be composed of typical desmosomal as well as adherens junction ... ...

    Abstract In contrast to epithelial cells, cardiomyocytes are connected by complex hybrid-type adhering junctions, termed composite junctions (areae compositae). Composite junctions are found to be composed of typical desmosomal as well as adherens junction proteins. Therefore, in adult mammalian cardiomyocytes desmosomal proteins are not restricted to the relatively small desmosomes but are indirectly involved in anchoring the myofibrillar actin filaments. Subsequent investigations revealed that the formation of composite junctions is a rather late event during mammalian development and vertebrate evolution. Nascent, more round shaped cardiomyocytes of early developmental stages are connected by desmosomes and separate adherens junctions quite similar to cells of epithelial origin. During progression of development both types of adhering junctions seem to gradually fuse at the two poles of the mature mammalian cardiomyocytes to establish the hybrid-type composite junctions. Recently, we could show that the specialized cardiomyocyte derived cells of the cardiac conduction system exhibit high amounts of desmosomes, not fully established composite junctions and adherens junctions. This underlines the fact that cells of the cardiac conduction system are known to resemble cardiomyocytes in their nascent state. However, the astonishing high amount of desmosomal protein containing adhering junctions connecting e.g., Purkinje fibers raises the possibility that pacemaker and conductive tissue may be affected by desmosomal gene mutations in ARVC/D patients.
    Keywords Heart ; area composita ; desmosome ; ARVC/D ; Conduction system ; Desmosomal gene mutation ; Physiology ; QP1-981 ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2012-02-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Conference proceedings: Once-Weekly Semaglutide 1 mg vs Empagliflozin 25 mg as Add-On to Metformin Monotherapy in Patients with Type 2 Diabetes: a Meta-Regression Analysis of Individual Patient Data

    Lingvay, Ildiko / Catarig, Andrei-Mircea / Sandberg, Anna / Lawson, Jack / Capehorn, Matthew / Pieperhoff, Sebastian / Johansen, Pierre / Shaw, Robert D. / Paine, Abby

    Diabetologie und Stoffwechsel

    2022  Volume 17, Issue S 01

    Event/congress Diabetes Kongress 2022 - 56. Jahrestagung der DDG, CityCube Berlin, 2022-05-25
    Language English
    Publishing date 2022-05-01
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article ; Conference proceedings
    ZDB-ID 2222993-0
    ISSN 1861-9010 ; 1861-9002
    ISSN (online) 1861-9010
    ISSN 1861-9002
    DOI 10.1055/s-0042-1746268
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  8. Article ; Online: Mutations with pathogenic potential in proteins located in or at the composite junctions of the intercalated disk connecting mammalian cardiomyocytes: a reference thesaurus for arrhythmogenic cardiomyopathies and for Naxos and Carvajal diseases.

    Rickelt, Steffen / Pieperhoff, Sebastian

    Cell and tissue research

    2012  Volume 348, Issue 2, Page(s) 325–333

    Abstract: In the past decade, an avalanche of findings and reports has correlated arrhythmogenic ventricular cardiomyopathies (ARVC) and Naxos and Carvajal diseases with certain mutations in protein constituents of the special junctions connecting the polar ... ...

    Abstract In the past decade, an avalanche of findings and reports has correlated arrhythmogenic ventricular cardiomyopathies (ARVC) and Naxos and Carvajal diseases with certain mutations in protein constituents of the special junctions connecting the polar regions (intercalated disks) of mature mammalian cardiomyocytes. These molecules, apparently together with some specific cytoskeletal proteins, are components of (or interact with) composite junctions. Composite junctions contain the amalgamated fusion products of the molecules that, in other cell types and tissues, occur in distinct separate junctions, i.e. desmosomes and adherens junctions. As the pertinent literature is still in an expanding phase and is obviously becoming important for various groups of researchers in basic cell and molecular biology, developmental biology, histology, physiology, cardiology, pathology and genetics, the relevant references so far recognized have been collected and are presented here in the following order: desmocollin-2 (Dsc2, DSC2), desmoglein-2 (Dsg2, DSG2), desmoplakin (DP, DSP), plakoglobin (PG, JUP), plakophilin-2 (Pkp2, PKP2) and some non-desmosomal proteins such as transmembrane protein 43 (TMEM43), ryanodine receptor 2 (RYR2), desmin, lamins A and C, striatin, titin and transforming growth factor-β3 (TGFβ3), followed by a collection of animal models and of reviews, commentaries, collections and comparative studies.
    MeSH term(s) Animals ; Arrhythmogenic Right Ventricular Dysplasia/etiology ; Arrhythmogenic Right Ventricular Dysplasia/genetics ; Arrhythmogenic Right Ventricular Dysplasia/metabolism ; Arrhythmogenic Right Ventricular Dysplasia/pathology ; Cardiomyopathies/etiology ; Cardiomyopathies/genetics ; Cardiomyopathies/metabolism ; Cardiomyopathy, Dilated ; Desmoglein 2/genetics ; Desmosomes/genetics ; Desmosomes/metabolism ; Desmosomes/pathology ; Disease Models, Animal ; Hair Diseases/etiology ; Hair Diseases/genetics ; Hair Diseases/metabolism ; Humans ; Keratoderma, Palmoplantar/etiology ; Keratoderma, Palmoplantar/genetics ; Keratoderma, Palmoplantar/metabolism ; Mutation
    Chemical Substances Desmoglein 2
    Language English
    Publishing date 2012-03-27
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 125067-x
    ISSN 1432-0878 ; 0302-766X
    ISSN (online) 1432-0878
    ISSN 0302-766X
    DOI 10.1007/s00441-012-1365-0
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  9. Article: The area composita of adhering junctions connecting heart muscle cells of vertebrates. VI. Different precursor structures in non-mammalian species.

    Pieperhoff, Sebastian / Franke, Werner W

    European journal of cell biology

    2008  Volume 87, Issue 7, Page(s) 413–430

    Abstract: Recent studies on the formation and molecular organization of the mammalian heart have emphasized the architectural and functional importance of the adhering junctions (AJs), which are densely clustered in the bipolar end regions (intercalated disks, IDs) ...

    Abstract Recent studies on the formation and molecular organization of the mammalian heart have emphasized the architectural and functional importance of the adhering junctions (AJs), which are densely clustered in the bipolar end regions (intercalated disks, IDs) connecting the elongated cardiomyocytes of the adult heart. Moreover, we learned from genetic studies of mutated AJ proteins that desmosomal proteins, which for the most part are integral components of ID-specific composite AJs (areae compositae, AC), are essential in heart development and function. Developmental studies have shown that the bipolar concentration of cardiomyocyte AJs in IDs is a rather late process and only completed postnatally. Here we report that in the adult hearts of diverse lower vertebrates (fishes, amphibia, birds) most AJs remain separate and distinct in molecular character, representing either fasciae adhaerentes, maculae adhaerentes (desmosomes) or--less frequently--some form of AC. In the mature hearts of the amphibian and fish species examined a large proportion of the AJs connecting cardiomyocytes is not clustered in the IDs but remains located on the lateral surfaces where they appear either as puncta adhaerentia or as desmosomes. In many places, these puncta connect parallel cardiomyocytes in spectacular ladder-like regular arrays (scalae adhaerentes) correlated with--and connected by--electron-dense plaque-like material to sarcomeric Z-bands. In the avian hearts, on the other hand, most AJs are clustered in the IDs but only a small proportion of the desmosomes appears as AC, compared to the dominance of distinct fasciae adhaerentes. We conclude that the fusion and amalgamation of AJs and desmosomes to ACs is a late process both in ontogenesis and in evolution. The significance and possible functional implications of the specific junctional structures in vertebrate evolution and the class-specific requirements of architectural and molecular assembly adaptation during regeneration processes are discussed.
    MeSH term(s) Adherens Junctions/physiology ; Amphibians/physiology ; Animals ; Antibodies/pharmacology ; Biological Evolution ; Cells, Cultured ; Chickens/physiology ; Columbidae/physiology ; Desmoplakins/immunology ; Desmoplakins/metabolism ; Eels/physiology ; Heart/physiology ; Microscopy, Electron ; Models, Biological ; Myocytes, Cardiac/physiology ; Myocytes, Cardiac/ultrastructure ; Oncorhynchus mykiss/physiology ; Plakophilins/immunology ; Plakophilins/metabolism ; Species Specificity ; Vertebrates/physiology ; Zebrafish/physiology
    Chemical Substances Antibodies ; Desmoplakins ; Plakophilins
    Language English
    Publishing date 2008-07
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 391967-5
    ISSN 1618-1298 ; 0171-9335 ; 0070-2463
    ISSN (online) 1618-1298
    ISSN 0171-9335 ; 0070-2463
    DOI 10.1016/j.ejcb.2008.02.005
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  10. Article: The area composita of adhering junctions connecting heart muscle cells of vertebrates - IV: coalescence and amalgamation of desmosomal and adhaerens junction components - late processes in mammalian heart development.

    Pieperhoff, Sebastian / Franke, Werner W

    European journal of cell biology

    2007  Volume 86, Issue 7, Page(s) 377–391

    Abstract: In the adult mammalian heart, the cardiomyocytes and thus their terminally anchored myofibrillar bundles are connected by large arrays of closely spaced or even fused adhering junctions (AJs), termed "intercalated disks" (IDs). In recent years, the ID ... ...

    Abstract In the adult mammalian heart, the cardiomyocytes and thus their terminally anchored myofibrillar bundles are connected by large arrays of closely spaced or even fused adhering junctions (AJs), termed "intercalated disks" (IDs). In recent years, the ID complex has attracted special attention as it has become clear that several human hereditary cardiomyopathies are caused by mutations of genes encoding ID marker proteins, in particular some that are also known as constituents of epithelial desmosomes. Previously, we have shown that in the mature myocardial ID the compositional differences between desmosome-like and adhaerens junctions are, by and large, lost and a composite hybrid structure, the area composita, is formed. We now report results from immunofluorescence and (immuno-)electron microscopic studies of heart formation during mouse embryogenesis and postnatal growth and show that the formation of the IDs with extended area composita structures is a late, primarily postnatal process. While up to birth small distinct desmosomes and AJs are resolved as predominant ID structures, areae compositae of increasing sizes and merged marker protein patterns occupy most of the IDs in the mature heart. Differences in the patterns of ID formation and amalgamation of the two ensembles of junction proteins in time and space are also demonstrated. Together with corresponding observations during rat and human heart development our results indicate that ID topogenesis and area composita formation are also late developmental processes in other mammals. We discuss the importance of the ID and the areae compositae in cardiac functions and, consequently, in cardiomyopathies and possible myocardial regeneration processes.
    MeSH term(s) Adherens Junctions/metabolism ; Adherens Junctions/ultrastructure ; Animals ; Desmosomes/metabolism ; Desmosomes/ultrastructure ; Heart/embryology ; Heart/growth & development ; Humans ; Mice ; Microscopy, Fluorescence ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/ultrastructure ; Rats ; Vertebrates/metabolism
    Language English
    Publishing date 2007-07
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 391967-5
    ISSN 1618-1298 ; 0171-9335 ; 0070-2463
    ISSN (online) 1618-1298
    ISSN 0171-9335 ; 0070-2463
    DOI 10.1016/j.ejcb.2007.04.001
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