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      New drug targets for type 2 diabetes and the metabolic syndrome.

      Nature

      metabolism, drug effects, Transcription Factors, Signal Transduction, Receptors, Cytoplasmic and Nuclear, Obesity, Metabolic Syndrome X, Liver, Lipid Metabolism, secretion, Insulin, therapeutic use, pharmacology, Hypoglycemic Agents, Humans, Glucose, Forecasting, drug therapy, Diabetes Mellitus, Type 2, Diabetes Mellitus, Animals

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          Abstract

          An insidious increase in features of the 'metabolic syndrome' - obesity, insulin resistance and dyslipidaemia -- has conspired to produce a worldwide epidemic of type 2 insulin-resistant diabetes mellitus. Most current therapies for this disease were developed in the absence of defined molecular targets or an understanding of disease pathogenesis. Emerging knowledge of key pathogenic mechanisms, such as the impairment of glucose-stimulated insulin secretion and the role of 'lipotoxicity' as a probable cause of hepatic and muscle resistance to insulin's effects on glucose metabolism, has led to a host of new molecular drug targets. Several have been validated through genetic engineering in mice or the preliminary use of lead compounds and therapeutic agents in animals and humans.

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          Journal
          10.1038/414821a
          11742415

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