Physiological effects of manipulating AMPK signalling genes

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The AMP activated protein kinase is a metabolic stress sensing protein kinase responsible for matching the supply of energy to the body's functions. During exercise it senses metabolic stress (reduction in energy) caused by muscle contraction and switches on metabolic processes to restore energy. This includes stimulating glucose uptake and burning fat. With training the AMP activated protein kinase also controls genes to adapt the body to future exercise. Reducing caloric intake activates the AMP activated protein kinase to suppress energy consuming activities and modify the expression of genes. This enzyme is a powerful regulator of lipid metabolism, inhibiting both cholesterol and triglyceride synthesis. Many conditions that activate the AMP activated protein kinase (exercise, reduced caloric intake) are associated with a healthy lifestyle, increased longevity and resistance to age onset diseases including cardiovascular disease (atherosclerosis, hypertension), obesity, neurodegeneration and diabetes. It has been found that metformin and rosiglitizone, major drugs used to treat people with type II diabetes activate the AMP activated protein kinase. By manipulating the genes for the AMP-activated protein kinase in mice we expect to gain new insights into the physiological roles of this enzyme and how it functions to protect the body from age onset diseases.