Tumor necrosis factor alpha inhibits signaling from the insulin receptor.

Association between insulin resistance, body mass and neopterin concentrations

“…Other factors, such as genetic predisposition for example in addition to obesity will be necessary to develop NIDDM [1,15]. Recently, TNF-a produced by adipocytes of the obese state has been reported to induce insulin resistance of NIDDM by inhibiting the activity of tyrosine kinase of the insulin receptor b-subunit, specifically in muscle and fat tissue [2,3]. In our study, there was a significant correlation between neopterin concentrations and BMI and also between neopterin and glucose concentrations.…”

“…Recent data from multiple experimental models of obesity suggested a key role of tumor necrosis factor-a (TNF-a) in insulin resistance of NIDDM. From the data it seems likely that elevated TNF-a produced by adipocytes of the obese state may inhibit the activity of tyrosine kinase of the insulin receptor b-subunit, specifically in muscle and fat tissue [2,3]. TNF-a is mainly produced by endotoxin-stimulated macrophages.…”

TNF‐α inhibits glucose‐induced insulin secretion in a pancreatic β‐cell line (INS‐1)

“…cfi~ted with type I and type II diabetes mellitus [1,[8][9][10][11][12]. While destruction offl-cells by cytokines may be responsible for type I ~iabetes, cytokines appear to play a multifaceted role in type II diabetes.…”

Diet but not aerobic exercise training reduces skeletal muscle TNF-a in overweight humans

“…However, TNF-α inhibits the activity of the insulin receptor and some of its downstream effectors. Cell culture experiments have demonstrated that insulin-induced tyrosine phosphorylation of the β-subunit of the insulin receptor and IRS-1 are reduced in the presence of TNF-α [3,27]. TNF-α promotes serine phosphorylation of IRS-1, which interferes with insulin-induced tyrosine phosphorylation and subsequent insulin signalling and action [28,29].…”