Phosphatidylinositol 3,4,5-Trisphosphate Phosphatase SKIP Links Endoplasmic Reticulum Stress in Skeletal Muscle to Insulin Resistance.

Abstract

Insulin resistance is critical in the pathogenesis of type 2 diabetes. Endoplasmic reticulum (ER) stress in liver and adipose tissues plays an important role in the development of insulin resistance. Although skeletal muscle is a primary site for insulin-dependent glucose disposal, it is unclear if ER stress in those tissues contributes to insulin resistance. In this study, we show that skeletal muscle kidney-enriched inositol polyphosphate phosphatase (SKIP), a PIP3 (phosphatidylinositol-3,4,5-trisphosphate) phosphatase, links ER stress to insulin resistance in skeletal muscle. SKIP expression was increased due to ER stress and was higher in the skeletal muscle isolated from high-fat-diet-fed mice and db/db mice than in that from wild-type mice. Mechanistically, ER stress promotes activating transcription factor 6 (ATF6) and X-box binding protein 1 (XBP1)-dependent expression of SKIP. These findings underscore the specific and prominent role of SKIP in the development of insulin resistance in skeletal muscle.

• Authors: Takeshi Ijuin, Tetsuya Hosooka, Tadaomi Takenawa
• Journal: Molecular and cellular biology (Mol Cell Biol) Vol. 36 Issue 1 Pg. 108-18 (Jan 01 2016) ISSN: 1098-5549 [Electronic] United States
• PMID: 26483413 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Insulin
• Phosphatidylinositol Phosphates
• phosphatidylinositol 3,4,5-triphosphate
• Pps protein, mouse
• Phosphoric Monoester Hydrolases

Topics

• Adipose Tissue
• Animals
• Diabetes Mellitus, Type 2 (enzymology)
• Diet, High-Fat (adverse effects)
• Endoplasmic Reticulum Stress (physiology)
• Insulin (metabolism)
• Insulin Resistance (physiology)
• Mice
• Mice, Transgenic
• Muscle, Skeletal (enzymology)
• Phosphatidylinositol Phosphates (metabolism)
• Phosphoric Monoester Hydrolases (genetics, metabolism)