Protection Against Insulin Resistance by Apolipoprotein M/Sphingosine-1-Phosphate.

Abstract:

:Subjects with low serum HDL cholesterol levels are reported to be susceptible to diabetes, with insulin resistance believed to be the underlying pathological mechanism. Apolipoprotein M (apoM) is a carrier of sphingosine-1-phosphate (S1P), a multifunctional lipid mediator, on HDL, and the pleiotropic effects of HDL are believed to be mediated by S1P. In the current study, we attempted to investigate the potential association between apoM/S1P and insulin resistance. We observed that the serum levels of apoM were lower in patients with type 2 diabetes and that they were negatively correlated with BMI and the insulin resistance index. While deletion of apoM in mice was associated with worsening of insulin resistance, overexpression of apoM was associated with improvement of insulin resistance. Presumably, apoM/S1P exerts its protective effect against insulin resistance by activating insulin signaling pathways, such as the AKT and AMPK pathways, and also by improving the mitochondrial functions through upregulation of SIRT1 protein levels. These actions of apoM/S1P appear to be mediated via activation of S1P1 and/or S1P3. These results suggest that apoM/S1P exerts protective roles against the development of insulin resistance.

journal_name

Diabetes

journal_title

Diabetes

authors

Kurano M,Tsukamoto K,Shimizu T,Kassai H,Nakao K,Aiba A,Hara M,Yatomi Y

doi

10.2337/db19-0811

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

867-881

issue

5

eissn

0012-1797

issn

1939-327X

pii

db19-0811

journal_volume

69

pub_type

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