Partners in Crime: Beta-Cells and Autoimmune Responses Complicit in Type 1 Diabetes Pathogenesis

Toren, Eliana; Burnette, KaLia S.; Banerjee, Ronadip R.; Hunter, Chad S.; Tse, Hubert M.

doi:10.3389/fimmu.2021.756548

Cited by 58 publications

(31 citation statements)

References 217 publications

(228 reference statements)

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“…Type 1 diabetes mellitus is caused by an absolute (or almost absolute) lack of insulin due to autoimmune destruction of pancreatic β-cells, which leads to insulin insufficiency and hyperglycemia[ 10 ]. Conversely, type 2 diabetes mellitus is characterized by insulin resistance with an inadequately compensatory increase in insulin secretion[ 11 ].…”

Section: Diabetes and Immune Response Against Infectionsmentioning

confidence: 99%

Growing importance of urogenital candidiasis in individuals with diabetes: A narrative review

Talapko¹,

Meštrović²,

Škrlec³

2022

World J Diabetes

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Both diabetes and fungal infections contribute significantly to the global disease burden, with increasing trends seen in most developed and developing countries during recent decades. This is reflected in urogenital infections caused by Candida species that are becoming ever more pervasive in diabetic patients, particularly those that present with unsatisfactory glycemic control. In addition, a relatively new group of anti-hyperglycemic drugs, known as sodium glucose cotransporter 2 inhibitors, has been linked with an increased risk for colonization of the urogenital region with Candida spp., which can subsequently lead to an infectious process. In this review paper, we have highlighted notable virulence factors of Candida species (with an emphasis on Candida albicans ) and shown how the interplay of many pathophysiological factors can give rise to vulvovaginal candidiasis, potentially complicated with recurrences and dire pregnancy outcomes. We have also addressed an increased risk of candiduria and urinary tract infections caused by species of Candida in females and males with diabetes, further highlighting possible complications such as emphysematous cystitis as well as the risk for the development of balanitis and balanoposthitis in (primarily uncircumcised) males. With a steadily increasing global burden of diabetes, urogenital mycotic infections will undoubtedly become more prevalent in the future; hence, there is a need for an evidence-based approach from both clinical and public health perspectives.

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Section: Diabetes and Immune Response Against Infectionsmentioning

confidence: 99%

Growing importance of urogenital candidiasis in individuals with diabetes: A narrative review

Talapko¹,

Meštrović²,

Škrlec³

2022

World J Diabetes

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“…Despite significant advances in the pathophysiology of the illness, the etiology of T1D development remains a mystery 3 . Type 1 diabetes is the most frequent type of diabetes in children, accounting for roughly 75 percent of new diabetes diagnoses in patients under the age of 19. According to epidemiological research, the incidence of autoimmune diabetes in people aged 30-49 years is now at least as high as in young adults aged 15 to19 years 4 .…”

Section: Introductionmentioning

confidence: 99%

The Effect of Insulin Loaded Nanoparticles on Immuno-reactivity of Beta Cells in Rats with Diabetes Type 1

Shaaban¹,

Amr

Mohamadin

et al. 2023

Azhar International Journal of Pharmaceutical and Medical Scien

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The basic criteria of type 1 diabetes (T1D) are autoimmune destruction of beta cells that eventually leads to a full loss of insulin secretion capability, which is a crucial stage in the disease's pathophysiology. In recent investigations, it was shown that pancreatic tissues from long-term T1D patients included insulin-producing beta cells. These findings suggested the presence of working beta cells that had evaded apoptosis by lowering gene expression. The development of diabetic liver damage has been linked to oxidative stress, the formation of reactive oxygen species (ROS), and diabetes infections linked to beta-cell dysfunction. Other diabetes-related effects include immune-histochemical evaluation of the pancreas in male Wistar rats following oral treatment of insulin-loaded nanoparticles (INS) containing carboxymethyl chitosan nanoparticles (CMCNPs) and gold nanoparticles (AuNPs) independently. Because of their inhibitory and protective impact, beta cells' immunological reactivity was dramatically boosted as compared to the diabetic group, and a reduction in pancreatic inflammation was noted. In conclusion, promising effects of insulinloaded carboxymethyl chitosan NPs (INS-CMCNPs) and insulin-loaded gold NPs (INS-AuNPs) in controlling and promoting organ functions when compared to subcutaneous insulin were observed. This may provide new evidence for the reversibility of beta-cell dysfunction and insulin insufficiency with precise glycaemic control.

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“…As disease complexity continues to unfold, there is a growing appreciation for βcell dysfunction mechanisms in both pathologies. 2 Concomitantly, diabetes can be defined as a bi-hormonal disease due to hypersecretion by glucagon-producing αcells and thus lack of postprandial glucagon suppression in diabetic patients. 3 Both cell types reside within the pancreatic islets of Langerhans, clusters of cells embedded in the exocrine pancreas that cohesively function in endocrine and paracrine fashions to sense and tightly regulate glucose homeostasis.…”

Section: Introductionmentioning

confidence: 99%

“…Diabetes is broadly defined by the loss of functional insulin‐producing β‐cells via autoimmune destruction in Type 1, and by insulin resistance associated with β‐cell dysfunction and dedifferentiation in Type 2. As disease complexity continues to unfold, there is a growing appreciation for β‐cell dysfunction mechanisms in both pathologies 2 . Concomitantly, diabetes can be defined as a bi‐hormonal disease due to hypersecretion by glucagon‐producing α‐cells and thus lack of postprandial glucagon suppression in diabetic patients 3 .…”

Section: Introductionmentioning

confidence: 99%

The Ldb1 transcriptional co‐regulator is required for establishment and maintenance of the pancreatic endocrine lineage

et al. 2022

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Pancreatic islet cell development is regulated by transcription factors (TFs) that mediate embryonic progenitor differentiation toward mature endocrine cells. Prior studies from our lab and others showed that the islet‐enriched TF, Islet‐1 (Isl1), interacts with the broadly‐expressed transcriptional co‐regulator, Ldb1, to regulate islet cell maturation and postnhyperatal function (by embryonic day (E)18.5). However, Ldb1 is expressed in the developing pancreas prior to Isl1 expression, notably in multipotent progenitor cells (MPCs) marked by Pdx1 and endocrine progenitors (EPs) expressing Neurogenin‐3 (Ngn3). MPCs give rise to the endocrine and exocrine pancreas, while Ngn3+ EPs specify pancreatic islet endocrine cells. We hypothesized that Ldb1 is required for progenitor identity in MPC and EP populations during development to impact islet appearance and function. To test this, we generated a whole‐pancreas Ldb1 knockout, termed Ldb1ΔPanc, and observed severe developmental and postnatal pancreas defects including disorganized progenitor pools, a significant reduction of Ngn3‐expressing EPs, Pdx1HI β‐cells, and early hormone+ cells. Ldb1ΔPanc neonates presented with severe hyperglycemia, hypoinsulinemia, and drastically reduced hormone expression in islets, yet no change in total pancreas mass. This supports the endocrine‐specific actions of Ldb1. Considering this, we also developed an endocrine‐enriched model of Ldb1 loss, termed Ldb1ΔEndo. We observed similar dysglycemia in this model, as well as a loss of islet identity markers. Through in vitro and in vivo chromatin immunoprecipitation experiments, we found that Ldb1 occupies key Pdx1 and Ngn3 promoter domains. Our findings provide insight into novel regulation of endocrine cell differentiation that may be vital toward improving cell‐based diabetes therapies.

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Partners in Crime: Beta-Cells and Autoimmune Responses Complicit in Type 1 Diabetes Pathogenesis

Cited by 58 publications

References 217 publications

Growing importance of urogenital candidiasis in individuals with diabetes: A narrative review

Growing importance of urogenital candidiasis in individuals with diabetes: A narrative review

The Effect of Insulin Loaded Nanoparticles on Immuno-reactivity of Beta Cells in Rats with Diabetes Type 1

The Ldb1 transcriptional co‐regulator is required for establishment and maintenance of the pancreatic endocrine lineage

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