Bile acid TUDCA improves insulin clearance by increasing the expression of insulin-degrading enzyme in the liver of obese mice

Bile acid TUDCA improves insulin clearance by increasing the expression of insulin-degrading enzyme in the liver of obese mice

Disruption of insulin secretion and clearance both contribute to obesity-induced hyperinsulinemia, though reduced insulin clearance seems to be the main factor. The liver is the major site for insulin degradation, a process mainly coordinated by the insulin-degrading enzyme (IDE). The beneficial eff...

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Published in:Scientific reports Vol. 7; no. 1; pp. 14876 - 9
Main Authors: Vettorazzi, Jean Franciesco, Kurauti, Mirian Ayumi, Soares, Gabriela Moreira, Borck, Patricia Cristine, Ferreira, Sandra Mara, Branco, Renato Chaves Souto, Michelone, Luciana de Souza Lima, Boschero, Antonio Carlos, Junior, Jose Maria Costa, Carneiro, Everardo Magalhães
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01-11-2017
Nature Publishing Group
Subjects:
1-Phosphatidylinositol 3-kinase
13/1
631/443/319
64/60
692/163/2743/393
82/80
AKT protein
Bile
Enzymes
High fat diet
Humanities and Social Sciences
Hyperinsulinemia
Insulin
Insulin secretion
Insulysin
Liver
multidisciplinary
Obesity
Science
Science (multidisciplinary)
Secretion
Taurine
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Summary:Disruption of insulin secretion and clearance both contribute to obesity-induced hyperinsulinemia, though reduced insulin clearance seems to be the main factor. The liver is the major site for insulin degradation, a process mainly coordinated by the insulin-degrading enzyme (IDE). The beneficial effects of taurine conjugated bile acid (TUDCA) on insulin secretion as well as insulin sensitivity have been recently described. However, the possible role of TUDCA in insulin clearance had not yet been explored. Here, we demonstrated that 15 days treatment with TUDCA reestablished plasma insulin to physiological concentrations in high fat diet (HFD) mice, a phenomenon associated with increased insulin clearance and liver IDE expression. TUDCA also increased IDE expression in human hepatic cell line HepG2. This effect was not observed in the presence of an inhibitor of the hepatic membrane bile acid receptor, S1PR2, nor when its downstream proteins were inhibited, including IR, PI3K and Akt. These results indicate that treatment with TUDCA may be helpful to counteract obesity-induced hyperinsulinemia through increasing insulin clearance, likely through enhanced liver IDE expression in a mechanism dependent on S1PR2-Insulin pathway activation.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-13974-0