| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1985: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Insulin ragulates a variety of cell functions by binding to a specific receptor embedded in plasma membrane. Insulin-receptor is composed of <alpha> and <beta> -subunits. <alpha> -subunit is responsible for the binding and <beta> -subunit has protein kinase activity which is specific to tyrosine-residue. By the binding of insulin to receptor complex, auto-phosphorylation of <beta> -subunit has been demonstrated. However, it is controversial whether this auto-phosphorylation is the prime step for transmitting the signal of insulin binding. In addition to the auto-phosphorylation, phosphorylation of plasma membrane proteins or cytoskeleton proteins has been observed depending on insulin and it is not clear which phosphorylation is the most important.
Various cellular functions have been demonstrated to be regulated by insulin. These include 1) transport of nutrients, such as sugars and amino acids, is stimulated by insulin, 2) anabolism of carbohydrates, lipids and amino acids is stimulated by insulin, and 3) proliferation of many cells in culture is stimulated by insulin. Considering such a variety of effects, it is more reasonable to assume many signal-transmitting mechanisms by which insulin regulate cellular functions.
In order to find out better experimental systems to analyze the signal-transmitting mechanism of insulin, regulation of the expression of carbamoyl-phosphate synthetase gene (a urea cycle enzyme) in hepatoma cells and in primary cultured hepatocytes was studied. Supression of the gene expression of a urea cycle enzyme by insulin was demonstrated for the first time. A multiple-regulation of a urea cycle enzyme by glucocorticoids, glucagon and catecholamines was found. Effect of factors including insulin on the adipose conversion of 3T3-L1 was also analyzed. By this analysis, an important progress was made concerning the regulation of obesity.
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