GLUT-4, tumor necrosis factor, essential fatty acids and daf-genes and their role in insulin resistance and non-insulin dependent diabetes mellitus.
It is now believed that the GLUT-4 receptor, tumor necrosis factor-alpha (TNF-alpha), essential fatty acids (EFAs) and their metabolites and daf-genes have an important role in the development of obesity and non-insulin dependent diabetes mellitus (NIDDM). The protein encoded by daf-2 is 35% identical to the human insulin receptor, daf-7 codes a transforming growth factor-beta (TGF-beta) type signal and daf-16 can enhance superoxide dismutase (SOD) expression. EFAs and their metabolites can alter the cell membrane fluidity and enhance the expression of GLUT-4 and insulin receptors. EFAs can suppress TNF-alpha production and secretion, a mechanism that may have relevance to the role of these fatty acids in the pathogenesis of insulin resistance, obesity and NIDDM. Melatonin has anti-oxidant actions similar to daf-16, TGF-beta and SOD. Based on this evidence, it is proposed that GLUT-4, TNF-alpha, EFAs, daf-genes, melatonin and leptin interact with each other in ways which may have relevance to the development or abrogation of insulin resistance, obesity, NIDDM, complications due to NIDDM, longevity and ageing.
D029742:Caenorhabditis elegans Proteins; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005228:Fatty Acids, Essential / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D020738:Leptin; D008550:Melatonin / Q000378:metabolism; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins / Q000502:physiology*; D005810:Multigene Family / Q000502:physiology*; D009124:Muscle Proteins; D011506:Proteins / Q000378:metabolism; D011972:Receptor, Insulin / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*