In type 1 diabetes mellitus (T1DM), T cell-mediated destruction of insulin-producing pancreatic beta cells leads to the acute onset of hyperglycemia. The nonobese diabetic mouse model of human T1DM reveals that T cells capable of inducing diabetes can escape normal central tolerance, and can cause T1DM if left unchecked. However, several regulatory T cell subsets can temper autoaggressive T cel...

Polygenic type 2 diabetes in mouse models is associated with obesity and results from a combination of adipogenic and diabetogenic alleles. Here we report the identification of a candidate gene for the diabetogenic effect of a QTL (Nidd/SJL, Nidd1) contributed by the SJL, NON, and NZB strains in outcross populations with New Zealand Obese (NZO) mice. A critical interval of distal chromosome 4 (...

OBJECTIVE The pancreatic microenvironment is considered to be the primary location of autoreactive T-cells in type 1 diabetes. Diabetogenic T-cells have also been detected in the spleens of NOD mice. However, it is not known whether bone marrow also contains T-cells specific for self-antigens in hosts with autoimmunity. In this study, we investigated whether autoreactive diabetogenic T-cells ar...

Autoreactive T cells infiltrating the target organ can possess a broad TCR affinity range. However, the extent to which such biophysical parameters contribute to T cell pathogenic potential remains unclear. In this study, we selected eight InsB9-23-specific TCRs cloned from CD4(+) islet-infiltrating T cells that possessed a relatively broad range of TCR affinity to generate NOD TCR retrogenic m...

Dehydroascorbic acid has been shown to produce diabetes (1, 2). In this respect it is similar to alloxan (3). Whereas alloxan has not yet been shown to occur physiologically, dehydroascorbic acid is accepted as occurring under physiological conditions in the cells of animals (4). Therefore, it is important to study the factors that are known to affect alloxan diabetes in order to determine thei...

From Table 2 it will also be seen that the diabetogenic dose of alloxan in normal animals, as found in this laboratory, ranges between 130 and 140 mg./kg. and the lethal dose is observed to be in the neighbourhood of 225 mg./kg. It is interesting to note that the diabetogenic and lethal doses of alloxan in acetoacetate-treated animals, having blood GSH in the neighbourhood of 3 mg./100 ml., are...

Preventing activation of diabetogenic T cells is critical for delaying type 1 diabetes onset. The inhibitory molecule lymphocyte activation gene 3 (LAG-3) and metalloprotease tumor necrosis factor-α converting enzyme (TACE) work together to regulate TH1 responses. The aim of this study was to determine if regulating redox using a catalytic antioxidant (CA) could modulate TACE-mediated LAG-3 she...

OBJECTIVE Apolipoprotein E (ApoE) regulates plasma lipid levels via modulation of lipolysis and serving as ligand for receptor-mediated clearance of triglyceride (TG)-rich lipoproteins. This study tested the impact of modulating lipid delivery to tissues on insulin responsiveness and diet-induced obesity. RESEARCH DESIGN AND METHODS ApoE(+/+) and apoE(-/-) mice were placed on high-fat-high-su...

The interaction between causative genes and diet is known to influence the onset of obesity and diabetes in humans, although it has remained difficult to identify diabetogenic gene(s) because humans are genetically and environmentally heterogeneous. Mouse SMXA recombinant inbred (RI) strains are established from parental inbred strains (SM/J and A/J) and have been shown to be beneficial tools f...