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The epidemic of obesity and type 2 diabetes mellitus is dramatically increasing. Environmental factors, such as sedentary life-style, hypercaloric, fat-rich diet and genetic susceptibility are considered major determinants of type 2 diabetes mellitus. Obesity and peripheral insulin resistance are hallmarks and major risk factors for development of type 2 diabetes mellitus. Cardiovascular complications (eg, atherosclerosis, coronary heart disease) of both metabolic disorders are associated with chronic subclinical inflammation.1 2 The low degree of inflammation in obesity and type 2 diabetes mellitus results from increased expression and production of cytokines and acute phase reactants such as C-reactive proteins, interleukins (ILs), tumour necrosis factor (TNF)α, or lipopolysaccharides (LPS).1 2 Inflammatory cytokines induce peripheral insulin resistance by impairing the insulin receptor (IR)-dependent signalling.1 2 For instance, experimental application of TNFα leads to the phosphorylation of the serine residues of the insulin receptor substrate-1 (IRS-1) with the consecutive inhibition of insulin-stimulated tyrosine autophosphorylation of the IR. The consequence of the impaired IR signalling is a blunted glucose uptake by peripheral tissues. The resulting chronic hyperglycaemia causes deleterious effects on pancreatic beta-cell function and morphology. Inflammatory cytokines reduce insulin secretion, induce apoptosis of pancreatic beta-cells in type 2 diabetes mellitus.3 Administration of anti-inflammatory agents (eg, high doses of aspirin) or experimental deletion of receptors for inflammatory cytokines results in increased insulin sensitivity and improved pancreatic beta-cell function, which is paralleled by a reduction of hyperglycaemia and loss of body weight.4 5 Despite numerous studies describing the activation …
Competing interests: None declared.
Funding: MZS was supported by the DFG (STR 558/6-1).