Disruption of the mitochondria-associated ER membrane (MAM) plays a central role in palmitic acid–induced insulin resistance

Satoko Shinjo, Shuying Jiang, Masaaki Nameta, Tomohiro Suzuki, Mai Kanai, Yuta Nomura, Nobuhito Goda

研究成果: Article

15 引用 (Scopus)

抄録

The mitochondria-associated ER membrane (MAM) is a specialized subdomain of ER that physically connects with mitochondria. Although disruption of inter-organellar crosstalk via the MAM impairs cellular homeostasis, its pathological significance in insulin resistance in type 2 diabetes mellitus remains unclear. Here, we reveal the importance of reduced MAM formation in the induction of fatty acid–evoked insulin resistance in hepatocytes. Palmitic acid (PA) repressed insulin-stimulated Akt phosphorylation in HepG2 cells within 12 h. Treatment with an inhibitor of the ER stress response failed to restore PA-mediated suppression of Akt activation. Mitochondrial reactive oxygen species (ROS) production did not increase in PA-treated cells. Even short-term exposure (3 h) to PA reduced the calcium flux from ER to mitochondria, followed by a significant decrease in MAM contact area, suggesting that PA suppressed the functional interaction between ER and mitochondria. Forced expression of mitofusin-2, a critical component of the MAM, partially restored MAM contact area and ameliorated the PA-elicited suppression of insulin sensitivity with Ser473 phosphorylation of Akt selectively improved. These results suggest that loss of proximity between ER and mitochondria, but not perturbation of homeostasis in the two organelles individually, plays crucial roles in PA-evoked Akt inactivation in hepatic insulin resistance.

元の言語English
ページ(範囲)86-93
ページ数8
ジャーナルExperimental Cell Research
359
発行部数1
DOI
出版物ステータスPublished - 2017 10 1

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Insulin Resistance
Mitochondria
Palmitic Acid
Membranes
Homeostasis
Phosphorylation
Hep G2 Cells
Organelles
Type 2 Diabetes Mellitus
Hepatocytes
Reactive Oxygen Species
Insulin
Calcium
Liver

ASJC Scopus subject areas

  • Cell Biology

これを引用

Disruption of the mitochondria-associated ER membrane (MAM) plays a central role in palmitic acid–induced insulin resistance. / Shinjo, Satoko; Jiang, Shuying; Nameta, Masaaki; Suzuki, Tomohiro; Kanai, Mai; Nomura, Yuta; Goda, Nobuhito.

:: Experimental Cell Research, 巻 359, 番号 1, 01.10.2017, p. 86-93.

研究成果: Article

Shinjo, Satoko ; Jiang, Shuying ; Nameta, Masaaki ; Suzuki, Tomohiro ; Kanai, Mai ; Nomura, Yuta ; Goda, Nobuhito. / Disruption of the mitochondria-associated ER membrane (MAM) plays a central role in palmitic acid–induced insulin resistance. :: Experimental Cell Research. 2017 ; 巻 359, 番号 1. pp. 86-93.
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