Human beta cell mass and function in diabetes: Recent advances in knowledge and technologies to understand disease pathogenesis
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TLDR
In type 1 and type 2 diabetes impairment of beta cell function is an early feature of disease pathogenesis while a substantial decrease in beta cell mass occurs more closely to clinical manifestation, which suggests that the development of novel strategies for protection and recovery ofBeta cell function could be most promising for successful diabetes treatment and prevention.Abstract:
Background
Plasma insulin levels are predominantly the product of the morphological mass of insulin producing beta cells in the pancreatic islets of Langerhans and the functional status of each of these beta cells. Thus, deficiency in either beta cell mass or function, or both, can lead to insufficient levels of insulin, resulting in hyperglycemia and diabetes. Nonetheless, the precise contribution of beta cell mass and function to the pathogenesis of diabetes as well as the underlying mechanisms are still unclear. In the past, this was largely due to the restricted number of technologies suitable for studying the scarcely accessible human beta cells. However, in recent years, a number of new platforms have been established to expand the available techniques and to facilitate deeper insight into the role of human beta cell mass and function as cause for diabetes and as potential treatment targets.read more
Citations
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Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes
Peter Thompson,Ajit Shah,Vasilis Ntranos,Vasilis Ntranos,Frédéric Van Gool,Mark A. Atkinson,Anil Bhushan +6 more
TL;DR: It is shown that during the natural history of T1D in humans and the non-obese diabetic (NOD) mouse model, a subset of beta cells acquires a senescence-associated secretory phenotype (SASP), and clearance of senescent beta cells could be a new therapeutic approach for T1d.
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From NASH to diabetes and from diabetes to NASH: Mechanisms and treatment options
Amalia Gastaldelli,Kenneth Cusi +1 more
TL;DR: The altered pathophysiological mechanisms that underlie the development of type 2 diabetes in NAFLD and vice versa are discussed and pharmacological agents currently available to treat T2D that could potentially be useful for the management of NASH are discussed.
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Type 1 and 2 diabetes mellitus: A review on current treatment approach and gene therapy as potential intervention.
Sin Yee Tan,Joyce Ling Mei Wong,Yan Jinn Sim,Su Sie Wong,Safa Abdelgadir Mohamed Elhassan,Sean Hong Tan,Grace Pei Ling Lim,Nicole Wuen Rong Tay,Naveenya Chetty Annan,Subrat Kumar Bhattamisra,Mayuren Candasamy +10 more
TL;DR: An overview of the current conventional medications in diabetes, discovery of newer pharmacological drugs and gene therapy as a potential intervention of diabetes in the future is delivered.
Journal ArticleDOI
A Map of Human Type 1 Diabetes Progression by Imaging Mass Cytometry
Nicolas Damond,Stefanie Engler,Vito R T Zanotelli,Denis Schapiro,Clive Wasserfall,Irina Kusmartseva,Harry S. Nick,Fabrizio Thorel,Pedro Luis Herrera,Mark A. Atkinson,Bernd Bodenmiller +10 more
TL;DR: Analysis of islets from 12 human donors using imaging mass cytometry revealed that β cell destruction is preceded by a β cell marker loss and by recruitment of cytotoxic and helper T cells in type 1 diabetes.
Journal ArticleDOI
Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?)
TL;DR: The evidence that β-cells are active participants in the dialogue with the immune system during the development of type 1 diabetes mellitus is examined and it is suggested that therapies targeting β-cell health, vitality and function might prove essential, in combination with immunotherapy, to change the course of events leading to β- cell destruction.
References
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Pre-Type I Diabetes: Linear Loss of Beta Cell Response to Intravenous Glucose
TL;DR: Twenty-one intravenous (i.v.) glucose tolerance tests were performed on nine subjects before the onset of overt type I diabetes mellitus and elevated levels of la-positive T-lymphocytes and Islet cell antibodies were detected during the prediabetic period.
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TL;DR: Analysis of the transcriptomes of human exocrine and endocrine pancreatic cell types revealed previously unrecognised gene expression patterns in these cell types, including transcriptional regulators HOPX and HDAC9 in the human beta cell population.
Journal ArticleDOI
Age-Dependent Pancreatic Gene Regulation Reveals Mechanisms Governing Human β Cell Function
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Single-cell transcriptomes reveal characteristic features of human pancreatic islet cell types.
Jin Li,Johanna Klughammer,Matthias Farlik,Thomas Penz,Andreas Spittler,Charlotte Barbieux,Ekaterine Berishvili,Christoph Bock,Christoph Bock,Christoph Bock,Stefan Kubicek +10 more
TL;DR: To dissect the cellular composition of the human pancreatic islet and to establish transcriptomes for all major cell types, single‐cell RNA sequencing is performed on 70 cells sorted from human primary tissue to validate previously described marker genes at the single‐ cell level and to identify specifically expressed transcription factors for all islet cell subtypes.