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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.
This article was published in the following journal.
Name: PloS one
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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).
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