Splenocytes from nonobese diabetic mice overexpressing murine IL (mIL)-4 upon recombinant retrovirus infection lose their capacity to transfer diabetes to nonobese diabetic-scid recipients. Diabetes appeared in 0-20% of mice injected with mIL-4-transduced cells vs 80-100% of controls injected with beta-galactosidase-transduced cells. Protected mice showed a majority of islets (60%) presenting w...

Intravenous injection of alloxan into rabbits, rats, dogs, monkeys, etc., produces a brief hyperglycemia, then a transient hypoglycemia, which in the case of rabbits is severe enough to cause convulsions and death, unless counteracted by repeated injections of glucose, and finally a permanent diabetic hyperglycemia. The cause of the transient hypoglycemia has had various explanations. Goldner a...

OBJECTIVE Obesity is associated with insulin resistance, chronic low-grade inflammation, and atherosclerosis. Toll-like receptor 4 (TLR4) participates in the cross talk between inflammation and insulin resistance, being activated by both lipopolysaccharide and saturated fatty acids. The present study was undertaken to determine whether TLR4 deficiency has a protective role in inflammation, insu...

Autoimmune diabetes results from a breakdown of self-tolerance that leads to T cell-mediated beta-cell destruction. Abnormal maturation and other defects of dendritic cells (DCs) have been associated with the development of diabetes. Evidence is accumulating that self-tolerance can be restored and maintained by semimature DCs induced by GM-CSF. We have investigated whether GM-CSF is a valuable ...

Classical major histocompatibility complex (MHC) class I and II molecules present peptides to cognate T-cell receptors on the surface of T lymphocytes. The specificity with which T cells recognize peptide-MHC (pMHC) complexes has allowed for the utilization of recombinant, multimeric pMHC ligands for the study of minute antigen-specific T-cell populations. In type 1 diabetes (T1D), CD8+ cytotox...

To localize the MHC-linked diabetogenic genes in the nonobese diabetic (NOD) mouse, a recombinational hotspot from the B10.A(R209) mouse was introduced to the region between the MHC class I K and class II A of the NOD mouse with the recombinational site centromeric to the Lmp2/Tap1 complex by breeding the two strains. Replacement of the NOD region centromeric to the recombinational site with th...

Immunologically privileged sites express Fas ligand (FasL), which protects them from attack by activated T cells that express Fas and die upon contact with FasL. In an attempt to protect nonobese diabetic mice (NOD) from autoimmune diabetes, we made FasL transgenic NOD mice using the beta cell-specific rat insulin-1 promoter. Surprisingly, these transgenic mice showed heightened sensitivity to ...

position of l-methyl-l-nitrosourea, a bone marrow toxin in animals, results in the formation of a nonmyelosuppressive but diabetogenic antitumor agent streptozotocin (10). An additional observation was the identification of a class of NO nitrosoureas and nitrosamine compounds with a R@!!4@ (C H 2)12H end group that depresses pyridine nucleotide concentrations in liver, the proposed mechanism of...

Amylin, a peptide copackaged with insulin in beta-cell granules, was measured in the effluent of the perfused rat pancreases by means of a newly developed specific radioimmunoassay. Its secretion parallels that of insulin in response to 20 mM glucose, 10 mM arginine, or the combination thereof. The relative molar amount of secreted amylin was estimated to be 25-37% that of insulin. Treatment wi...