The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, low concentrations of interleukin 1 β.

07:00 EST 13th February 2020 | BioPortfolio

Summary of "The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, low concentrations of interleukin 1 β."

A central and still open question regarding the pathogenesis of autoimmune diseases, such as type 1 diabetes, concerns the processes that underlie the generation of MHC-presented autoantigenic epitopes that become targets of autoimmune attack. Proteasomal degradation is a key step in processing of proteins for MHC class I presentation. Different types of proteasomes can be expressed in cells dictating the repertoire of peptides presented by the MHC class I complex. Of particular interest for type 1 diabetes is the proteasomal configuration of pancreatic β cells, as this might facilitate autoantigen presentation by β cells and thereby their T-cell mediated destruction. Here we investigated whether so-called inducible subunits of the proteasome are constitutively expressed in β cells, regulated by inflammatory signals and participate in the formation of active intermediate or immuno-proteasomes. We show that inducible proteasomal subunits are constitutively expressed in human and rodent islets and an insulin-secreting cell-line. Moreover, the β5i subunit is incorporated into active intermediate proteasomes that are bound to 19S or 11S regulatory particles. Finally, inducible subunit expression along with increase in total proteasome activities are further upregulated by low concentrations of IL-1β stimulating proinsulin biosynthesis. These findings suggest that the β cell proteasomal repertoire is more diverse than assumed previously and may be highly responsive to a local inflammatory islet environment.


Journal Details

This article was published in the following journal.

Name: PloS one
ISSN: 1932-6203
Pages: e0222432


DeepDyve research library

PubMed Articles [20626 Associated PubMed Articles listed on BioPortfolio]

IL-6 is present in beta and alpha cells in human pancreatic islets: Expression is reduced in subjects with type 1 diabetes.

IL-6 is a pro-inflammatory cytokine upregulated in some autoimmune diseases. The role of IL-6 in the development of type 1 diabetes (T1D) is unclear. Clinical studies are investigating whether tociliz...

Immunoreactivity of cytotoxic T-lymphocyte antigen 2 alpha in mouse pancreatic islet cells.

Cells of the pancreatic islets produce several molecules including insulin (beta cells), glucagon (alpha cells), somatostatin (delta cells), pancreatic polypeptide (PP cells), ghrelin (epsilon cells),...

B7-1 drives TGF-β stimulated pancreatic carcinoma cell migration and expression of EMT target genes.

B7-1 proteins are routinely expressed on the surface of antigen presenting cells (APC) and within the innate immune system. They function to establish a biologically optimal and dynamic balance betwee...

Serum miR-204 is an early biomarker of type 1 diabetes-associated pancreatic beta-cell loss.

Pancreatic beta-cell death is a major factor in the pathogenesis of type 1 diabetes (T1D), but straightforward methods to measure beta-cell loss in humans are lacking underlining the need for novel bi...

Protective effects of Cer and Ytt Ox NPs and Nan Se on H2O2-induced oxidative stress in pancreatic Beta cells.

Type 1 diabetes mellitus (T1DM) is characterized by the destruction of insulin-producing Beta cells in the pancreas. Researchers hope that islet transplantation will help to patients with IDDM.

Clinical Trials [11934 Associated Clinical Trials listed on BioPortfolio]

Randomized, Controlled Trial to Test the Efficacy of Interferon Beta in the Treatment of Intermediate Uveitis

The purpose of this study is to investigate if interferon beta is superior to the standard treatment with Methotrexate for the treatment of intermediate uveitis and macular edema.

Role of TMEM219 Marker in Type 1 Diabetes

Type 1 diabetes (T1D) is a chronic metabolic disease characterized by autoimmune destruction of β cells of the insulin producing pancreatic islets. The different immunological approaches ...

A Study of Mesothelin Redirected Autologous T Cells for Advanced Pancreatic Carcinoma

Pancreatic carcinoma typically has a high recurrence rate and very poor prognosis. Surgery is the best choice for the treatment of pancreatic cancer, but for those advanced pancreatic canc...

Beta-Cell Function and Sitagliptin Trial (BEST)

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by progressive deterioration in the function of the pancreatic beta-cells, which are the cells that produce an...

Pharmacodynamic Biomarkers to Support Biosimilar Development: Interferon Beta-1A Products

This study is designed to assess pharmacokinetics and pharmacodynamics of interferon beta-1a and peginterferon beta-1a across an appropriate dose range to inform clinical trial operating c...

Medical and Biotech [MESH] Definitions

Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).

Cell surface proteins that bind pancreatic hormones with high affinity and trigger intracellular changes which influence the behavior of cells. These include receptors for glucagon (secreted by alpha cells), insulin (secreted by beta cells), somatostatin (secreted by delta cells), and pancreatic peptide (secreted by PP cells). Some of these hormones and receptors also support neurotransmission.

Peptide hormones secreted into the blood by cells in the ISLETS OF LANGERHANS of the pancreas. The alpha cells secrete glucagon; the beta cells secrete insulin; the delta cells secrete somatostatin; and the PP cells secrete pancreatic polypeptide.

A benign tumor of the pancreatic ISLET CELLS. Usually it involves the INSULIN-producing PANCREATIC BETA CELLS, as in INSULINOMA, resulting in HYPERINSULINISM.

A receptor for GLUCAGON-LIKE PEPTIDE 1 (GLP-1) expressed primarily on the surface of beta and ductal exocrine cells of the pancreas, as well as cells of other tissues. GLP-1 acts through GLP-1R to potentiate signaling in pancreatic cells in response to glucose-stimulated insulin secretion (GSIS).

Quick Search

DeepDyve research library

Relevant Topics

Pancreatitis Acute pancreatitis is inflammation of the pancreas caused by the release of activated pancreatic enzymes. Common triggers are biliary tract disease and chronic heavy alcohol intake.  Diagnosis is based on clinical presentation...

Autoimmune Disorders
Autoimmune disorders are conditions that occurs when the immune system mistakenly attacks and destroys healthy body tissue. There are more than 80 different types of autoimmune disorders. Normally the immune system's white blood cells help protect ...

Diabetes is a lifelong condition that causes a person's blood sugar level to become too high. The two main types of diabetes are: type 1 diabetes type 2 diabetes In the UK, diabetes affects approximately 2.9 million people. There are a...

Searches Linking to this Article