Relevance of fatty acid modulation of GSIS in the pathogenesis of insulin resistance and type 2 diabetes

While on the one hand fatty acid-mediated increases in insulin secretion may be important in ensuring adequate insulin release in situations where both FFA and glucose are elevated, on the other hand chronic over-exposure to fatty acids could lead to hypersecretion of insulin and hyperinsulinaemia. Boden (1997) propose that in non-diabetic and moderately insulin-resistant subjects, FFA stimulation of gluconeogenesis is counteracted by the FFA stimulation of insulin secretion, and is thereby an important counter-regulatory mechanism for maintaining circulating glucose concentration. However, in the development of type 2 diabetes in obese subjects, FFAs fail to stimulate the required compensatory insulin response, resulting in peripheral under-utilisation and hepatic overproduction of glucose, with resultant hyperglycaemia.

It has been proposed that chronic over-exposure to FFA and LC acyl CoA results in the accumulation of lipid components within the beta-cell, with lipotoxicity and apoptosis leading to possible failure in insulin biosynthesis and secretion (Roduit et al., 2004). This beta cell failure typifies severe type 2 diabetes and explains the fact that many of these subjects ultimately require insulin treatment to bring their glucose intolerance under control. A model of beta-cell lipotoxicity based on over-expression of SREBP-1c in INS-1 cells has been developed (Yamashita et al., 2004). This model showed lipotoxicity was associated with enhanced expression of lipogenic genes, e.g. acetyl CoA carboxylase, TAG accumulation, and a reduction in the ATP : ADP ratio. Such investigations provide evidence for possible mechanisms involved in the chronic effects of over-provision of dietary lipid on insulin resistance, although studies are required to elucidate the mechanisms involved when this stage of insulin resistance is reached.

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Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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