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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

Acute effects of fatty acids on insulin secretion from rat and human islets of Langerhans.

TL;DR: Acute effects of a range of fatty acids on insulin secretion from rat and human islets of Langerhans at different glucose concentrations support the view that fatty acids play an important role in glucose homeostasis during undernutrition.
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Insulin Resistance Alters Islet Morphology in Nondiabetic Humans

TL;DR: The data in this series of studies suggest that neogenesis from duct cells and transdifferentiation of α-cells are potential contributors to the β-cell compensatory response to insulin resistance in the absence of overt diabetes.
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Natural History of β-Cell Function in Type 1 Diabetes

TL;DR: Understanding the modifiers and predictors of beta-cell function would allow targeting immunological approaches to those individuals most likely to benefit from therapy, as well as emphasized the importance of residual insulin production for glycemic control and prevention of end-organ complications.
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Functional Assessment of Pancreatic β-Cell Area in Humans

TL;DR: A C-peptide–to–glucose ratio after oral glucose ingestion appears to better predict β-cell area than fasting measures, such as the HOMA index, which is closely related to pancreatic β- cell area in humans.
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