Transgenic tumor necrosis factor (TNF)-alpha production in pancreatic islets leads to insulitis, not diabetes. Distinct patterns of inflammation in TNF-alpha and TNF-beta transgenic mice.
Tumour necrosis factor alpha (TNF) mRNA expression has been reported to be up-regulated in adipose tissue from several rodent models of obesity and diabetes and from obese humans.
Tumour necrosis factor alpha (TNF alpha) is a candidate gene for the development of obesity, which in turn is a major risk factor for diabetes mellitus.
Islet-specific expression of IL-10 promotes diabetes in nonobese diabetic mice independent of Fas, perforin, TNF receptor-1, and TNF receptor-2 molecules.
These polymorphisms appear to be of biological importance as individual alleles have been associated with higher production of TNF and/or an increased risk of rheumatoid arthritis or diabetes mellitus.
In conclusion, the -308G/A polymorphism in the TNF promoter is strongly associated with the risk of diabetes but not cardiovascular mortality in old age.
Lower rate of tumor necrosis factor-alpha -863A allele and higher concentration of tumor necrosis factor-alpha receptor 2 in first-degree relatives of subjects with type 2 diabetes.
After adjusting for BMI and other lifestyle factors, all three biomarkers significantly predicted diabetes risk; the odds ratios (ORs) comparing extreme quintiles were 1.64 (95% CI 1.10-2.45) for TNF-alphaR2, 1.91 (1.27-2.86) for IL-6, and 4.36 (2.80-6.80) for CRP (P for trend <0.001 for all biomarkers).
The present study was undertaken to investigate lipopolysaccharide-induced production of tumour necrosis factor (TNF)-alpha in monocytes from patients with type 2 diabetes and to assess its relationship with diabetes-associated metabolic abnormalities.
Mediators of inflammation such as tumor necrosis factor-alpha, interleukin (IL)-1beta, the IL-6 family of cytokines, IL-18, and certain chemokines have been proposed to be involved in the events causing both forms of diabetes.
Adjusted for TNF-alpha and IL-1beta polymorphisms, patients with a IL-6 (-174)CC genotype have a 3.0-fold (95% CI: 1.2-7.1) increased risk of developing diabetes before the age of 6 years than (-174)G allele carrier patients.
Of all TMA+ patients, EIA- patients were more likely to have diabetes, be on dialysis therapy longer, and have lower liver enzyme levels and higher proinflammatory cytokine levels, including tumor necrosis factor alpha and interleukin 6.
Results showed that: (1) IL-10 production was lower; (2) IL-10 ICC was reduced; (3) B7-H1-expressing CD19(+) cells were diminished; and (4) TNFalpha production and ICC by CD4(+) T cells was augmented in DM patients.
After stratification according to risk factors for CAD, our analysis revealed that CAD patients with diabetes (p=0.042) and CAD patients without hypertension (p= 0.0495) displayed a higher frequency of the TNF -308 AA genotype compared with healthy controls.
Selective expression of HO-1 prevented TNF- and hyperglycemia-mediated superoxide (O2-) formation, DNA degeneration, and upregulation of caspase, but increased the expression of pAkt and Bcl-xL, proteins responsible for endothelial dysfunction in diabetes.
It has recently been reported that tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) plays various roles in such autoimmune diseases as diabetes, multiple sclerosis (MS), and systemic lupus erythematosus (SLE).