Abstract:
:At least 57 independent loci within the human genome confer varying degrees of risk for the development of type 1 diabetes (T1D). The majority of these variants are thought to contribute to overall genetic risk by modulating host innate and adaptive immune responses, ultimately resulting in a loss of immunological tolerance to β cell antigens. Early efforts to link specific risk variants with functional alterations in host immune responses have employed animal models or genotype-selected individuals from clinical bioresource banks. While some notable genotype:phenotype associations have been described, there remains an urgent need to accelerate the discovery of causal variants and elucidate the molecular mechanisms by which susceptible alleles alter immune functions. One significant limitation has been the inability to study human T1D risk loci on an isogenic background. The advent of induced pluripotent stem cells (iPSCs) and genome-editing technologies have made it possible to address a number of these outstanding questions. Specifically, the ability to drive multiple cell fates from iPSC under isogenic conditions now facilitates the analysis of causal variants in multiple cellular lineages. Bioinformatic analyses have revealed that T1D risk genes cluster within a limited number of immune signaling pathways, yet the relevant immune cell subsets and cellular activation states in which candidate risk genes impact cellular activities remain largely unknown. In this review, we summarize the functional impact of several candidate risk variants on host immunity in T1D and present an isogenic disease-in-a-dish model system for interrogating risk variants, with the goal of expediting precision therapeutics in T1D.
journal_name
Front Endocrinol (Lausanne)journal_title
Frontiers in endocrinologyauthors
Wallet MA,Santostefano KE,Terada N,Brusko TMdoi
10.3389/fendo.2017.00276subject
Has Abstractpub_date
2017-10-18 00:00:00pages
276issn
1664-2392journal_volume
8pub_type
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2011.00084
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abstract::Graves' disease (GD) is an organ-specific autoimmune disease, and thyrotropin (TSH) receptor (TSHR) is a major autoantigen in this condition. Since the extracellular domain of human TSHR (TSHR-ECD) is shed into the circulation, TSHR-ECD is a preferentially immunogenic portion of TSHR. Both genetic factors and environm...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2016.00120
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doi:10.3389/fendo.2020.00228
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abstract::Objective: To clarify the role and mechanism of miR-17-92 cluster in islet beta-cell repair after streptozotocin intervention. Methods: Genetically engineered mice (miR-17-92βKO) and control RIP-Cre mice were intraperitoneally injected with multiple low dose streptozotocin. Body weight, random blood glucose (RBG), fas...
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pub_type: 杂志文章
doi:10.3389/fendo.2020.00009
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abstract::Some newly described steroid-related compounds, also found in the rest of the body, are formed and active in the central nervous system, particularly in the brain. Some are of pharmacological and physiopathological interest. We specifically report on two compounds, "MAP4343," a new neurosteroid very efficient antidepr...
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pub_type: 杂志文章
doi:10.3389/fendo.2018.00316
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abstract::Accumulating evidence shows that H2S has physiological functions in various tissues and organs. It includes regulation of neuronal activity, vascular tension, a release of insulin, and protection of the heart, kidney, and brain from ischemic insult. H2S is produced by enzymes from l-cysteine; cystathionine β-synthase,...
journal_title:Frontiers in endocrinology
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doi:10.3389/fendo.2013.00087
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abstract::Background: POU1F1 is an essential transcription factor for the differentiation, proliferation and survival of somatotrophs, lactotrophs, and thyrotrophs. Mutations in the POU1F1 gene are characterized by growth hormone (GH), thyrotropin, and prolactin deficiencies, commonly presenting with growth retardation and cent...
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doi:10.3389/fendo.2019.00381
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abstract::Background: Bologna criteria poor ovarian responders have a very low prognosis. Although, it has been proposed that LH supplementation could be beneficial in women with previous hypo-response to FSH. There are no studies comparing the cumulative live birth rates (LBRs) between corifollitropin alfa (CFA) and highly pur...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00175
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abstract::The insulin signaling pathway is a modulator of metabolism in insects and can regulate functions associated with growth and development, as well as lipid and carbohydrate balance. We have previously reported the presence of an insulin-like peptide and an insulin-like growth factor in Rhodnius prolixus, which are invol...
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doi:10.3389/fendo.2018.00745
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
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abstract::Osteocytes are the most abundant (~95%) cells in bone with the longest half-life (~25 years) in humans. In the past osteocytes have been regarded as vestigial cells in bone, since they are buried inside the tough bone matrix. However, during the last 30 years it has become clear that osteocytes are as important as bon...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2020.00405
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abstract::Diabetes is a worldwide public health concern as it is associated with various complications. One of the major complications of diabetes is diabetic foot syndrome that results in catastrophic events such as ulceration and amputation. Therefore, the main four strategies of diabetic foot care involve risk prediction, pr...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2020.00308
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abstract::Pituitary adenomas (PA) are amongst the most prevalent intracranial tumors, causing complications by hormonal overproduction or deficiency and tumor mass effects, with 95% of cases occurring sporadically. Associated germline mutations (AIP, MEN1, CDKN1B, PRKAR1A, SDHx) and Xq26.3 microduplications are increasingly ide...
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doi:10.3389/fendo.2019.00837
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abstract::Background: Associations between vitiligo and thyroid disorders have been suggested, However, the prevalence of thyroid disorders in vitiligo vary widely. Purpose: To conduct a systematic review and meta-analysis assessing the prevalence of thyroid disorders in patients with vitiligo. Method: The PubMed, Cochrane Libr...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00803
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abstract::The insulin-like growth factor (IGF) family plays key roles in growth and development. In the cornea, IGF family members have been implicated in proliferation, differentiation, and migration, critical events that maintain a smooth refracting surface that is essential for vision. The IGF family is composed of multiple ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2020.00024
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abstract::Obesity is a prominent metabolic disease that predisposes individuals to multiple comorbidities, including type 2 diabetes mellitus, cardiovascular diseases, and cancer. Elevated circulating levels of fatty acids contribute to the development of obesity, in part, by targeting the hypothalamus. Palmitate, the most abun...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.00351
更新日期:2020-06-12 00:00:00
abstract:BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver diseases closely associated with obesity and insulin resistance; deficient growth hormone (GH) action in liver has been implicated as a mechanism. Here, we investigated the evolution of NAFLD in aged mice with liver-sp...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2014.00218
更新日期:2014-12-18 00:00:00
abstract::As one of the most serious complications of diabetes, diabetic cardiomyopathy (DCM) imposes a huge burden on individuals and society, and represents a major public health problem. It has long been recognized that physical exercise has important health benefits for patients with type 2 diabetes, and regular physical ex...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2018.00729
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journal_title:Frontiers in endocrinology
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journal_title:Frontiers in endocrinology
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doi:10.3389/fendo.2020.587616
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2011.00114
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abstract::Licorice has been used as a medicinal plant from 2.500 years. It shows a wide range of biological and pharmacological activities, including anti-inflammatory and immune regulatory actions. One of its most known effects is the induction of hypertension, and it can induce what appears to be pseudohyperaldosteronism, due...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
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abstract::Responses to a high fat, high sucrose (HFHS) diet vary greatly among inbred strains of mice. We sought to examine the epigenetic (DNA methylation) changes underlying these differences as well as variation in weight loss when switched to a low-fat chow diet. We surveyed DNA methylation from livers of 45 inbred mouse st...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00882
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abstract:Background:It is well known that adiposity is a risk factor for insulin resistance and type 2 diabetes mellitus. In the present study, we aimed to investigate the associations of measures of adiposity with indices of glycemia and of glycemic variability over a 72-h period in non-diabetic older adults. Methods:This cro...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00238
更新日期:2018-05-14 00:00:00
abstract::O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants. In humans, dysregulation of O-GlcNAcylation occurs in a wide range of diseases, including cancer, diabetes, and neurodegeneration. Since its discovery more than 30 years ago, great ...
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doi:10.3389/fendo.2018.00606
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
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abstract::Background and Objectives: Clitoromegaly is an important parameter in the evaluation of ambiguous genitalia in neonates, but the normative data for clitoral size in newborns have racial/ethnic differences. The present study aimed to determine clitoral length (CL) and clitoral width (CW) values and establish cutoff mea...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.00297
更新日期:2020-06-03 00:00:00
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2011.00105
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