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  1. Article ; Online: Type 1 diabetes: what is the role of autoimmunity in β cell death?

    Donath, Marc Y

    The Journal of clinical investigation

    2022  Volume 132, Issue 20

    Abstract: The current dogma of type 1 diabetes pathogenesis asserts that an autoimmune attack leads to the destruction of pancreatic β cells, with subsequent hyperglycemia. This dogma is based on islet autoantibodies emerging prior to the onset of type 1 diabetes. ...

    Abstract The current dogma of type 1 diabetes pathogenesis asserts that an autoimmune attack leads to the destruction of pancreatic β cells, with subsequent hyperglycemia. This dogma is based on islet autoantibodies emerging prior to the onset of type 1 diabetes. In this issue of the JCI, Warncke et al. report on their investigation of the development of hyperglycemia below the diabetes threshold as an early proxy of β cell demise. Surprisingly, they found that an elevation in blood glucose preceded the appearance of autoimmunity. This observation calls into question the importance of autoimmunity as the primary cause of β cell destruction and has implications for prevention and treatment in diabetes.
    MeSH term(s) Autoantibodies ; Autoimmunity ; Blood Glucose ; Cell Death ; Diabetes Mellitus, Type 1/pathology ; Humans ; Hyperglycemia/pathology ; Insulin-Secreting Cells/pathology ; Islets of Langerhans
    Chemical Substances Autoantibodies ; Blood Glucose
    Language English
    Publishing date 2022-10-17
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI164460
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  2. Article ; Online: Designer cytokine for the treatment of diabetes.

    Donath, Marc Y

    Nature metabolism

    2020  Volume 1, Issue 10, Page(s) 933–934

    Language English
    Publishing date 2020-07-20
    Publishing country Germany
    Document type Journal Article
    ISSN 2522-5812
    ISSN (online) 2522-5812
    DOI 10.1038/s42255-019-0130-z
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  3. Article ; Online: Type 1 diabetes

    Marc Y. Donath

    The Journal of Clinical Investigation, Vol 132, Iss

    what is the role of autoimmunity in β cell death?

    2022  Volume 20

    Abstract: The current dogma of type 1 diabetes pathogenesis asserts that an autoimmune attack leads to the destruction of pancreatic β cells, with subsequent hyperglycemia. This dogma is based on islet autoantibodies emerging prior to the onset of type 1 diabetes. ...

    Abstract The current dogma of type 1 diabetes pathogenesis asserts that an autoimmune attack leads to the destruction of pancreatic β cells, with subsequent hyperglycemia. This dogma is based on islet autoantibodies emerging prior to the onset of type 1 diabetes. In this issue of the JCI, Warncke et al. report on their investigation of the development of hyperglycemia below the diabetes threshold as an early proxy of β cell demise. Surprisingly, they found that an elevation in blood glucose preceded the appearance of autoimmunity. This observation calls into question the importance of autoimmunity as the primary cause of β cell destruction and has implications for prevention and treatment in diabetes.
    Keywords Medicine ; R
    Language English
    Publishing date 2022-10-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Glucose or Insulin, Which Is the Culprit in Patients with COVID-19 and Diabetes?

    Donath, Marc Y

    Cell metabolism

    2020  Volume 33, Issue 1, Page(s) 2–4

    Abstract: Patients with a metabolic syndrome (overweight, diabetes, hypertension, and dyslipidemia) have a particularly bad outcome if infected with SARS-CoV-2. Yu et al. (2020) suggest that insulin therapy itself may promote fatality in patients with COVID-19 and ...

    Abstract Patients with a metabolic syndrome (overweight, diabetes, hypertension, and dyslipidemia) have a particularly bad outcome if infected with SARS-CoV-2. Yu et al. (2020) suggest that insulin therapy itself may promote fatality in patients with COVID-19 and diabetes.
    MeSH term(s) COVID-19/complications ; COVID-19/drug therapy ; COVID-19/metabolism ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/metabolism ; Female ; Glucose/metabolism ; Humans ; Inflammation/complications ; Inflammation/drug therapy ; Inflammation/metabolism ; Insulins/adverse effects ; Insulins/metabolism ; Insulins/therapeutic use ; Male ; SARS-CoV-2/metabolism
    Chemical Substances Insulins ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2020-11-24
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2176834-1
    ISSN 1932-7420 ; 1550-4131
    ISSN (online) 1932-7420
    ISSN 1550-4131
    DOI 10.1016/j.cmet.2020.11.015
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  5. Article ; Online: Inflammation and type 2 diabetes: from basic science to treatment.

    Donath, Marc Y

    Seminars in immunopathology

    2019  Volume 41, Issue 4, Page(s) 411–412

    MeSH term(s) Animals ; Biomedical Research ; Diabetes Mellitus, Type 2 ; Humans ; Inflammation
    Language English
    Publishing date 2019-06-25
    Publishing country Germany
    Document type Editorial
    ZDB-ID 2316828-6
    ISSN 1863-2300 ; 1863-2297
    ISSN (online) 1863-2300
    ISSN 1863-2297
    DOI 10.1007/s00281-019-00749-0
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  6. Article ; Online: Physiological role of cytokines in the regulation of mammalian metabolism.

    de Baat, Axel / Trinh, Beckey / Ellingsgaard, Helga / Donath, Marc Y

    Trends in immunology

    2023  Volume 44, Issue 8, Page(s) 613–627

    Abstract: The innate cytokine system is involved in the response to excessive food intake. In this review, we highlight recent advances in our understanding of the physiological role of three prominent cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis ... ...

    Abstract The innate cytokine system is involved in the response to excessive food intake. In this review, we highlight recent advances in our understanding of the physiological role of three prominent cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF), in mammalian metabolic regulation. This recent research highlights the pleiotropic and context-dependent functions in the immune-metabolic interplay. IL-1β is activated in response to overloaded mitochondrial metabolism, stimulates insulin secretion, and allocates energy to immune cells. IL-6 is released by contracting skeletal muscle and adipose tissue and directs energy from storing tissues to consuming tissues. TNF induces insulin resistance and prevents ketogenesis. Additionally, the therapeutic potential of modulating the activity of each cytokine is discussed.
    MeSH term(s) Animals ; Humans ; Cytokines/metabolism ; Interleukin-6/metabolism ; Adipose Tissue ; Tumor Necrosis Factor-alpha/metabolism ; Insulin Resistance/physiology ; Mammals
    Chemical Substances Cytokines ; Interleukin-6 ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2023-07-07
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2036831-8
    ISSN 1471-4981 ; 1471-4906
    ISSN (online) 1471-4981
    ISSN 1471-4906
    DOI 10.1016/j.it.2023.06.002
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  7. Article ; Online: Protocol for isolation and spectral flow cytometry analysis of immune cells from the murine exocrine and endocrine pancreas.

    Steiger, Laura / Baumann, Zora / Keller, Lena / Böni-Schnetzler, Marianne / Donath, Marc Y / Meier, Daniel T

    STAR protocols

    2023  Volume 4, Issue 4, Page(s) 102664

    Abstract: Diabetes mellitus is a disease of the hormone-secreting endocrine pancreas. However, increasing evidence suggests that the exocrine pancreas is also involved in the pathogenesis of diabetes. In this protocol, we describe how to harvest both isolated ... ...

    Abstract Diabetes mellitus is a disease of the hormone-secreting endocrine pancreas. However, increasing evidence suggests that the exocrine pancreas is also involved in the pathogenesis of diabetes. In this protocol, we describe how to harvest both isolated islets and exocrine tissue from one mouse pancreas, followed by a detailed explanation of how to isolate and analyze immune cells using full-spectrum flow cytometry.
    MeSH term(s) Mice ; Animals ; Flow Cytometry ; Islets of Langerhans ; Pancreas, Exocrine
    Language English
    Publishing date 2023-10-27
    Publishing country United States
    Document type Journal Article
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2023.102664
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  8. Article ; Online: Multiple benefits of targeting inflammation in the treatment of type 2 diabetes.

    Donath, Marc Y

    Diabetologia

    2016  Volume 59, Issue 4, Page(s) 679–682

    Abstract: ... 1007/s00125-016-3890-y ) and a commentary by the Session Chair, Piero Marchetti (DOI: 10.1007/s00125 ...

    Abstract The association between the metabolic syndrome and a pathological activation of the innate immune system is now well established. Thus, defective insulin secretion and action are due, at least in part, to islet, liver and fat inflammation in type 2 diabetes. Furthermore, an inflammatory process also seems to be involved in the development of cardiovascular, renal and ophthalmological complications of this disease. Interestingly, several other inflammatory diseases are associated with the metabolic syndrome, such as psoriasis, gout and rheumatic arthritis. The aim of this review is to discuss the clinical progress of anti-inflammatory drugs in the treatment of type 2 diabetes and then speculate on the possible further development of these drugs, with the aim of using the drugs in combination in order to combat the multiple manifestations of inflammatory diseases. This review summarises a presentation given at the 'Islet inflammation in type 2 diabetes' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Simone Baltrusch, DOI: 10.1007/s00125-016-3891-x , and Jerry Nadler and colleagues, DOI: 10.1007/s00125-016-3890-y ) and a commentary by the Session Chair, Piero Marchetti (DOI: 10.1007/s00125-016-3875-x ).
    MeSH term(s) Anti-Inflammatory Agents/therapeutic use ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/immunology ; Humans ; Inflammation/drug therapy ; Inflammation/immunology
    Chemical Substances Anti-Inflammatory Agents
    Language English
    Publishing date 2016-04
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 1694-9
    ISSN 1432-0428 ; 0012-186X
    ISSN (online) 1432-0428
    ISSN 0012-186X
    DOI 10.1007/s00125-016-3873-z
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    Zs.A 279: Show issues Location:
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  9. Article ; Online: Cystine/Glutamate antiporter system xc- deficiency impairs macrophage glutathione metabolism and cytokine production.

    de Baat, Axel / Meier, Daniel T / Fontana, Adriano / Böni-Schnetzler, Marianne / Donath, Marc Y

    PloS one

    2023  Volume 18, Issue 10, Page(s) e0291950

    Abstract: System xc-, encoded by Slc7a11, is an antiporter responsible for exporting glutamate while importing cystine, which is essential for protein synthesis and the formation of thiol peptides, such as glutathione. Glutathione acts as a co-factor for enzymes ... ...

    Abstract System xc-, encoded by Slc7a11, is an antiporter responsible for exporting glutamate while importing cystine, which is essential for protein synthesis and the formation of thiol peptides, such as glutathione. Glutathione acts as a co-factor for enzymes responsible for scavenging reactive oxygen species. Upon exposure to bacterial products, macrophages exhibit a rapid upregulation of system xc-. This study investigates the impact of Slc7a11 deficiency on the functionality of peritoneal and bone marrow-derived macrophages. Our findings reveal that the absence of Slc7a11 results in significantly reduced glutathione levels, compromised mitochondrial flexibility, and hindered cytokine production in bone marrow-derived macrophages. Conversely, system xc- has a lesser impact on peritoneal macrophages in vivo. These results indicate that system xc- is essential for maintaining glutathione levels, mitochondrial functionality, and cytokine production, with a heightened importance under atmospheric oxygen tension.
    MeSH term(s) Glutamic Acid/metabolism ; Cystine/metabolism ; Antiporters ; Macrophages, Peritoneal/metabolism ; Glutathione/metabolism ; Cytokines/metabolism ; Amino Acid Transport System y+/genetics ; Amino Acid Transport System y+/metabolism
    Chemical Substances Glutamic Acid (3KX376GY7L) ; Cystine (48TCX9A1VT) ; Antiporters ; Glutathione (GAN16C9B8O) ; Cytokines ; Amino Acid Transport System y+
    Language English
    Publishing date 2023-10-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0291950
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  10. Article ; Online: Inflammation in obesity, diabetes, and related disorders.

    Rohm, Theresa V / Meier, Daniel T / Olefsky, Jerrold M / Donath, Marc Y

    Immunity

    2022  Volume 55, Issue 1, Page(s) 31–55

    Abstract: Obesity leads to chronic, systemic inflammation and can lead to insulin resistance (IR), β-cell dysfunction, and ultimately type 2 diabetes (T2D). This chronic inflammatory state contributes to long-term complications of diabetes, including non-alcoholic ...

    Abstract Obesity leads to chronic, systemic inflammation and can lead to insulin resistance (IR), β-cell dysfunction, and ultimately type 2 diabetes (T2D). This chronic inflammatory state contributes to long-term complications of diabetes, including non-alcoholic fatty liver disease (NAFLD), retinopathy, cardiovascular disease, and nephropathy, and may underlie the association of type 2 diabetes with other conditions such as Alzheimer's disease, polycystic ovarian syndrome, gout, and rheumatoid arthritis. Here, we review the current understanding of the mechanisms underlying inflammation in obesity, T2D, and related disorders. We discuss how chronic tissue inflammation results in IR, impaired insulin secretion, glucose intolerance, and T2D and review the effect of inflammation on diabetic complications and on the relationship between T2D and other pathologies. In this context, we discuss current therapeutic options for the treatment of metabolic disease, advances in the clinic and the potential of immune-modulatory approaches.
    MeSH term(s) Animals ; Diabetes Complications/immunology ; Diabetes Mellitus, Type 2/immunology ; Humans ; Immunomodulation ; Inflammation/immunology ; Insulin Resistance ; Obesity/immunology
    Language English
    Publishing date 2022-01-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2021.12.013
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