Track topics on Twitter Track topics that are important to you
Imatinib (Gleevec) reverses type 1 diabetes (T1D) in NOD mice and is currently in clinical trials in individuals with recent-onset disease. While research has demonstrated that imatinib protects islet β cells from the harmful effects of ER stress, the role the immune system plays in its reversal of T1D has been less well understood, and specific cellular immune targets have not been identified. In this study, we demonstrate that B lymphocytes, an immune subset that normally drives diabetes pathology, are unexpectedly required for reversal of hyperglycemia in NOD mice treated with imatinib. In the presence of B lymphocytes, reversal was linked to an increase in serum insulin concentration, but not an increase in islet β cell mass or proliferation. However, improved β cell function was reflected by a partial recovery of MafA transcription factor expression, a sensitive marker of islet β cell stress that is important to adult β cell function. Imatinib treatment was found to increase the antioxidant capacity of B lymphocytes, improving reactive oxygen species (ROS) handling in NOD islets. This study reveals a novel mechanism through which imatinib enables B lymphocytes to orchestrate functional recovery of T1D β cells.
This article was published in the following journal.
Name: JCI insight
Scattered throughout the pancreas, the endocrine islets rely on neurovascular support for signal relay to regulate hormone secretion and for maintaining tissue homeostasis. The islet accessory cells (...
An insufficient adaptive beta-cell compensation is a hallmark of type 2 diabetes (T2D). Primary cilia function as versatile sensory antennae regulating various cellular processes, but their role on co...
IL-33/ST2 signal is important for the generation of forkhead box P3 (Foxp3) regulatory (Treg) cells, which contribute to immune homeostasis in the context of diseases. The aim of this study was to det...
Islet amyloid polypeptide (IAPP) misfolding and toxic oligomers contribute to beta cell loss and stress in type 2 diabetes. Pregnancy-related diabetes predicts subsequent risk for type 2 diabetes but ...
Type 1 diabetes mellitus (T1DM) results from an autoimmune destruction of insulin-producing beta cells in the islet of the endocrine pancreas. Although islet transplantation has been regarded as an id...
Islet Transplantation is a procedure used in people with difficult to control Type 1 Diabetes. Insulin producing cells (islets) are isolated from a deceased donor pancreas. After the cells...
The purpose of this study is to test whether the islet cell transplantation procedures and results from a previous study in Edmonton, Canada, can be repeated. The study also is designed to...
The purpose of this study is to determine the safety of transplanting human islet cells for controlling hyperglycemia in brittle and/or complex patients with type 1 diabetes. In addition,...
The purpose of the study is to determine whether E1 and G1 are safe and effective in the treatment of type 1 diabetes. Type 1 diabetes is an autoimmune disease, in which the immune system...
Prevalence of diabetes is increasing rapidly both in China and all over the world.Hyperglycemia is an important risk factor and major hazard to cardiovascular and cerebrovascular diseases ...
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
A primary malignant neoplasm of the pancreatic ISLET CELLS. Usually it involves the non-INSULIN-producing cell types, the PANCREATIC ALPHA CELLS and the pancreatic delta cells (SOMATOSTATIN-SECRETING CELLS) in GLUCAGONOMA and SOMATOSTATINOMA, respectively.
A benign tumor of the pancreatic ISLET CELLS. Usually it involves the INSULIN-producing PANCREATIC BETA CELLS, as in INSULINOMA, resulting in HYPERINSULINISM.
A zinc efflux transporter highly expressed by ISLET CELLS of the pancreas. It functions in the accumulation of zinc in intracellular vesicles and may be involved in INSULIN maturation and storage processes. Variations in the SLC30A8 gene are associated with susceptibility to DIABETES MELLITUS, TYPE 2.
A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...