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

Makoto Kurano1, Kazuhisa Tsukamoto2,3, Tomo Shimizu4

  • 1Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan kurano-tky@umin.ac.jp yatoyuta-tky@umin.ac.jp.

Diabetes
|January 10, 2020
PubMed

Insights

Apolipoprotein M (apoM) and sphingosine-1-phosphate (S1P) may protect against insulin resistance and type 2 diabetes. Lower apoM levels correlate with higher insulin resistance, while apoM enhances insulin signaling and mitochondrial function.

Area of Science:

  • Metabolic disease research
  • Lipidology
  • Endocrinology

Background:

  • Low high-density lipoprotein (HDL) cholesterol is linked to diabetes susceptibility.
  • Insulin resistance is a key pathological mechanism in diabetes.
  • Apolipoprotein M (apoM) carries sphingosine-1-phosphate (S1P) on HDL, mediating HDL's effects.

Purpose of the Study:

  • To investigate the association between apoM/S1P and insulin resistance.
  • To explore the role of apoM/S1P in the development of type 2 diabetes.

Main Methods:

  • Serum apoM levels were measured in patients with type 2 diabetes.
  • Correlation analysis was performed between apoM levels, BMI, and insulin resistance index.
  • ApoM deletion and overexpression studies were conducted in mice models.

Main Results:

  • Serum apoM levels were lower in type 2 diabetes patients.
  • Lower apoM levels negatively correlated with BMI and insulin resistance index.
  • ApoM deletion worsened insulin resistance, while overexpression improved it.

Conclusions:

  • ApoM/S1P exerts protective effects against insulin resistance.
  • Mechanisms include activation of AKT and AMPK pathways and improved mitochondrial function via SIRT1.
  • S1P receptors (S1P1/S1P3) mediate these protective actions.

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