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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
Author(s) -
Shih KuangChung,
Kwok ChingFai,
Ho LowTone
Publication year - 2000
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(20000801)78:2<231::aid-jcb6>3.0.co;2-o
Subject(s) - insulin receptor substrate , medicine , endocrinology , insulin receptor , insulin , irs2 , irs1 , receptor , chemistry , endothelin receptor , protein subunit , glucagon like peptide 1 receptor , insulin resistance , biology , biochemistry , agonist , gene
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 β‐subunit of the insulin receptor (IRβ) 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 IRβ 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 IRβ 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 IRβ/IRS‐1 expression. J. Cell. Biochem. 78:231–240, 2000. © 2000 Wiley‐Liss, Inc.