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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.

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Citations
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Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes

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

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.

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.
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A Map of Human Type 1 Diabetes Progression by Imaging Mass Cytometry

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.
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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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Journal ArticleDOI

Successful islet transplantation: continued insulin reserve provides long-term glycemic control.

TL;DR: The results indicate that prolonged insulin independence can be achieved after islet transplantation, and there are some risks associated acutely with the procedure, and hypercholesterolemia and hypertension are treatable concerns on longer-term follow-up.
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Assessment of Human Pancreatic Islet Architecture and Composition by Laser Scanning Confocal Microscopy

TL;DR: Analysis of islet architecture and composition using confocal laser scanning microscopy indicates that human islets not only are quite heterogeneous in terms of cell composition but also have a substantially different architecture from widely studied murine islets.
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Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects.

TL;DR: In obesity, although hypersecretion of insulin can be documented, the temporal pattern of secretion is largely unaltered, which suggests that the functioning beta cell mass is enhance, but normal regulatory mechanisms influencing secretion are still operative.
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Pancreatic beta-cell mass in European subjects with type 2 diabetes.

TL;DR: The average β‐cell mass is about 39% lower in T2D subjects compared with matched controls, and its decrease with duration of the disease could be a consequence of diabetes that, with further impairment of insulin secretion, contributes to the progressive deterioration of glucose homeostasis.
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Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients.

TL;DR: Japanese Type II diabetic patients show a reduction of beta-cell mass and evidence of increased oxidative stress-related tissue damage that is correlated with the extent of the beta- cell lesions.
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