New drug targets for type 2 diabetes and the metabolic syndrome.
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.
Moller
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Departments of Molecular Endocrinology and Metabolic Disorders, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005544:Forecasting; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D024821:Metabolic Syndrome; D009765:Obesity; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism
D007004:Hypoglycemic Agents; D007328:Insulin; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D005947:Glucose