| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
1999〜Search for thiazolidinedione-sensitive genes using GeneChip
Insulin sensitizer, thiazolidinedione, is thought to exert an antidiabetic effect by poteniating the insulin action chiefly on skeletal muscle cells. PPARg, a target of thiazolidinedione, is expressed in hepatocytes as well as adipocytes and muscle cells. To elucidate the mechanism of thiazolidinedione, effects of thiazolidinedione on gene expression of mouse hepatocytes were examined.
Mouse primary hepatocytes were incubated in medium in the presence or the absence of 5 μmol of rosiglitazone or 25 μmol of MCC555, a new thiazolidinedione. After 24 hr of culture, mRNA was purified from cultured hepatocytes. mRNA was labelled with fluoressence and was hybridized with GeneChip. Signals were compared among control, rosiglitazone and MCC55, and genes whose expressions were modified with thiazolidinedione were searched.
More than 20 genes including TC20874, TC21818, TC25018, TC26141, TC30984 were identified as genes whose expressi
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ons were upregulated with thiazolidinedione. On the other hand, more than 100 genes including TC14248, TC14302, TC14653, TC14842, TC15141 were identified as genes whose expression were downregulated with thiazolidinedione. Furtheremore, it was found that expression of VEGF was increased with troglitazone in cultured cellS and plasma VEGF levels were increased in human with prescribed troglitazone.
More than 20 genes including TC20874, TC21818, TC25018, TC26141, TC30984 were identified as genes whose expressions were upregulated with thiazolidinedione. On the other hand, more than 100 genes including TC14248, TC14302, TC14653, TC14842, TC15141 were identified as genes whose expression were downregulated with thiazolidinedione. Furtheremore, it was found that expression of VEGF was increased with troglitazone in cultured cellS and plasma VEGF levels were increased in human with prescribed troglitazone.
Though thiazolidinedione was reported to affect monocyte differentiation in vitro using cell lines, nothing is known about the effect on white blood cells when insulin sensitizer is clinically used. We, therefore, attempted to see changes of surface markers on white blood cells and serum cytokine levels from patient with type2 diabetes after pioglitazone, another kind of thiazolidinedione, was clinically used. We are now analyzing data. Less
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