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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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The ubiquitin-proteasome system and autophagy: self-digestion for metabolic health.

TL;DR: In this paper, the mutual regulation between the ubiquitin-proteasome system (UPS) and autophagy was described and the involvement of these two proteolytic systems in metabolic dysregulation, insulin resistance, and Type 2 diabetes mellitus.
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Long-term hyperglycemia aggravates α-synuclein aggregation and dopaminergic neuronal loss in a Parkinson’s disease mouse model

TL;DR: In this article , the authors investigated the effect of elevated blood glucose on the progression of Parkinson's disease in a transgenic mouse line (BAC-α-syn-GFP) overexpressing human α-syn.
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Impaired glucose-stimulated proinsulin secretion is an early marker of β-cell impairment before prediabetes stage.

TL;DR: This study suggests that impaired GSPS, but not impaired GSIS, may serve as an early biomarker to identify a subpopulation of NGT with a high-risk of diabetes.
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Long-term hyperglycemia aggravates α-synuclein aggregation and dopaminergic neuronal loss in a Parkinson’s disease mouse model

TL;DR: In this paper , the authors investigated the effect of elevated blood glucose on the progression of Parkinson's disease in a transgenic mouse line (BAC-α-syn-GFP) overexpressing human α-syn.
References
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Journal ArticleDOI

Homeostasis model assessment : insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man

TL;DR: The correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.
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Mechanisms linking obesity to insulin resistance and type 2 diabetes

TL;DR: In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors that are involved in the development of insulin resistance.
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β-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes

TL;DR: Since the major defect leading to a decrease in β-cell mass in type 2 diabetes is increased apoptosis, while new islet formation andβ-cell replication are normal, therapeutic approaches designed to arrest apoptosis could be a significant new development in the management of type 2 Diabetes.
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