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The standard progression moves through 5mg, 7.5mg, 10mg, 12.5mg and 15mg, with four weeks at each level before considering an increase

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This effect is associated with increased insulin signal transduction via phosphatidylinositol-3-OH kinase in the liver (but not in the skeletal muscle) and with reduced hepatic expression of the gluconeogenic genes, glucose-6-phosphatase and phosphoenolpyruvate kinase (German et al., Leptin, insulin, and nutrient-related signals in the CNS improve hepatic insulin sensitivity however, the mechanism by which CNS leptin signaling normalizes diabetic hyperglycemia and whether this process involves leptin-dependent effects on hepatic glucose production or tissue glucose uptake are unknown (German et al., ob/ob mice might be caused by the impairment of leptin signaling in pancreatic -cells and contributes to obesity and insulin resistance

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