Combined use of insulin and endothelin-1 causes decrease of protein expression of β-subunit of insulin receptor, insulin receptor substrate-1, and insulin-stimulated glucose uptake in rat adipocytes
✍ Scribed by Kuang-Chung Shih; Ching-Fai Kwok; Low-Tone Ho
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 204 KB
- Volume
- 78
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Previously, we reported that insulin-stimulated glucose uptake (ISGU) can be inhibited by endothelin (ET-1). However, the mechanism by which ET-1 impairs ISGU in adipocytes remains unclear. This study investigated the effects of ET-1 on insulin action in rat adipocytes in order to elucidate the molecular mechanism of action of ET-1 on ISGU. The results show that ISGU was increased fivefold after 3-h treatment with 1 nM insulin. Treatment with 100 nM ET-1 had no effect on basal glucose uptake. However, ET-1 inhibited approximately 25% of ISGU and 20% of insulin binding after 3-h treatment in the presence of 1 nM insulin. Expression of the -subunit of the insulin receptor (IR) and the insulin receptor substrate-1 (IRS-1) in adipocytes was not significantly affected by 1 nM insulin or by 100 nM ET-1, even after 3-h treatment. However, expressions of IR and IRS-1 were dramatically decreased in a dose-and time-dependent manner when adipocytes were treated with both insulin and ET-1. Approximately 50% of IR and 65% of IRS-1 expression levels were suppressed when adipocytes were simultaneously treated with both 1 nM insulin and 100 nM ET-1 for 3 h. These results suggest that the inhibitory effect of ET-1 on ISGU may be mediated via the insulin receptor and suppression of IR/IRS-1 expression.