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Type 2 diabetes is characterized by abnormal metabolism of glucose and fat, due in part to resistance to the actions of insulin in peripheral tissues. If untreated it leads to several complications such as blindness, kidney failure, neuropathy and amputations. The benefit of exercise in diabetic patients is well known and recent research indicates that AMP activated protein kinase (AMPK) plays a major role in this exercise related effect. AMPK is considered as a master switch regulating glucose and lipid metabolism. The AMPK is an enzyme that works as a fuel gauge, being activated in conditions of high energy phosphate depletion. AMPK is also activated robustly by skeletal muscle contraction and myocardial ischaemia, and is involved in the stimulation of glucose transport and fatty acid oxidation produced by these stimuli. In liver, activation of AMPK results in enhanced fatty acid oxidation and decreased production of glucose, cholesterol, and triglycerides. The two leading diabetic drugs namely, metformin and rosiglitazone, show their metabolic effects partially through AMPK. These data, along with evidence from studies showing that chemical activation of AMPK in vivo with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) improves blood glucose concentrations and lipid profiles, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes and other metabolic disorders.
Key words AMP kinase - diabetes - thiazolidinediones
Type 2 diabetes is characterized by the abnormal metabolism of glucose and fat, due in part to resistance to the actions of insulin in skeletal muscle, liver and fat. In the natural history of type 2 diabetes, pancreatic β-cells initially compensate for insulin resistance by secreting excess insulin. However with time, progressive β-cell failure leads to insulin deficiency and overt hyperglycaemia. Progression in diabetes leads to the development of chronic complications such as retinopathy, neuropathy and nephropathy, etc. At present, oral therapy for type 2 diabetes relies on several approaches targeted to reduce hyperglycaemia namely sulphonyl ureas, which increase insulin release from pancreatic islets; α-glucosidase inhibitors, which inhibit gut glucose absorption; metformin, which acts to reduce hepatic glucose output through inhibition of gluconeogenesis, peroxisome proliferators-activated receptor-ã activator thiazolidinediones (TZDs), which promote insulin sensitization. These therapies have either limited efficacy or significant mechanism based side effects like hypoglycaemia, flatulence, body weight gain or enhancement of gastrointestinal problems....