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

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2015 Oct 21

PMID 26483413

Citations 8

Authors

Takeshi Ijuin

Tetsuya Hosooka

Tadaomi Takenawa

Affiliations

Soon will be listed here.

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.

Citing Articles

Modulating PAK1: Accessory Proteins as Promising Therapeutic Targets.

Mirzaiebadizi A, Shafabakhsh R, Ahmadian M Biomolecules. 2025; 15(2).

PMID: 40001545 PMC: 11852631. DOI: 10.3390/biom15020242.

Glucosamine substituted sulfonylureas: IRS-PI3K-PKC-AKT-GLUT4 insulin signalling pathway intriguing agent.

Suaifan G, Alkhawaja B, Shehadeh M, Sharmaa M, Hor Kuan C, Okechukwu P RSC Med Chem. 2024; 15(2):695-703.

PMID: 38389876 PMC: 10880904. DOI: 10.1039/d3md00647f.

Atl (atlastin) regulates mTor signaling and autophagy in Drosophila muscle through alteration of the lysosomal network.

Srivastav S, van der Graaf K, Singh P, Utama A, Meyer M, McNew J Autophagy. 2023; 20(1):131-150.

PMID: 37649246 PMC: 10761077. DOI: 10.1080/15548627.2023.2249794.

Alteration of the N-methyladenosine methylation landscape in a mouse model of polycystic ovary syndrome.

Zou L, Li W, Xu D, Zhu S, Jiang B J Ovarian Res. 2023; 16(1):157.

PMID: 37550765 PMC: 10408202. DOI: 10.1186/s13048-023-01246-7.

Signaling pathways and intervention for therapy of type 2 diabetes mellitus.

Cao R, Tian H, Zhang Y, Liu G, Xu H, Rao G MedComm (2020). 2023; 4(3):e283.

PMID: 37303813 PMC: 10248034. DOI: 10.1002/mco2.283.

References

Haze K, Yoshida H, Yanagi H, Yura T, Mori K . Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol Biol Cell. 1999; 10(11):3787-99. PMC: 25679. DOI: 10.1091/mbc.10.11.3787. View

Cnop M, Foufelle F, Velloso L . Endoplasmic reticulum stress, obesity and diabetes. Trends Mol Med. 2011; 18(1):59-68. DOI: 10.1016/j.molmed.2011.07.010. View

Krook A, Bjornholm M, Galuska D, Jiang X, Fahlman R, Myers Jr M . Characterization of signal transduction and glucose transport in skeletal muscle from type 2 diabetic patients. Diabetes. 2000; 49(2):284-92. DOI: 10.2337/diabetes.49.2.284. View

Yoshida H, Okada T, Haze K, Yanagi H, Yura T, Negishi M . ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response. Mol Cell Biol. 2000; 20(18):6755-67. PMC: 86199. DOI: 10.1128/MCB.20.18.6755-6767.2000. View

Saltiel A . New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Cell. 2001; 104(4):517-29. DOI: 10.1016/s0092-8674(01)00239-2. View

Yoshida H, Matsui T, Yamamoto A, Okada T, Mori K . XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell. 2002; 107(7):881-91. DOI: 10.1016/s0092-8674(01)00611-0. View

Ijuin T, Takenawa T . SKIP negatively regulates insulin-induced GLUT4 translocation and membrane ruffle formation. Mol Cell Biol. 2003; 23(4):1209-20. PMC: 141139. DOI: 10.1128/MCB.23.4.1209-1220.2003. View

Rieusset J, Chauvin M, Durand A, Bravard A, Laugerette F, Michalski M . Reduction of endoplasmic reticulum stress using chemical chaperones or Grp78 overexpression does not protect muscle cells from palmitate-induced insulin resistance. Biochem Biophys Res Commun. 2011; 417(1):439-45. DOI: 10.1016/j.bbrc.2011.11.135. View

Samuel V, Shulman G . Mechanisms for insulin resistance: common threads and missing links. Cell. 2012; 148(5):852-71. PMC: 3294420. DOI: 10.1016/j.cell.2012.02.017. View

10.

Ijuin T, Takenawa T . Regulation of insulin signaling and glucose transporter 4 (GLUT4) exocytosis by phosphatidylinositol 3,4,5-trisphosphate (PIP3) phosphatase, skeletal muscle, and kidney enriched inositol polyphosphate phosphatase (SKIP). J Biol Chem. 2012; 287(10):6991-9. PMC: 3293580. DOI: 10.1074/jbc.M111.335539. View

11.

Ijuin T, Takenawa T . Regulation of insulin signaling by the phosphatidylinositol 3,4,5-triphosphate phosphatase SKIP through the scaffolding function of Pak1. Mol Cell Biol. 2012; 32(17):3570-84. PMC: 3422014. DOI: 10.1128/MCB.00636-12. View

12.

Kawasaki N, Asada R, Saito A, Kanemoto S, Imaizumi K . Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue. Sci Rep. 2012; 2:799. PMC: 3495279. DOI: 10.1038/srep00799. View

13.

Salvado L, Coll T, Gomez-Foix A, Salmeron E, Barroso E, Palomer X . Oleate prevents saturated-fatty-acid-induced ER stress, inflammation and insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism. Diabetologia. 2013; 56(6):1372-82. DOI: 10.1007/s00125-013-2867-3. View

14.

Ijuin T, Hatano N, Hosooka T, Takenawa T . Regulation of insulin signaling in skeletal muscle by PIP3 phosphatase, SKIP, and endoplasmic reticulum molecular chaperone glucose-regulated protein 78. Biochim Biophys Acta. 2015; 1853(12):3192-201. DOI: 10.1016/j.bbamcr.2015.09.009. View

15.

Gurung R, Tan A, Ooms L, McGrath M, Huysmans R, Munday A . Identification of a novel domain in two mammalian inositol-polyphosphate 5-phosphatases that mediates membrane ruffle localization. The inositol 5-phosphatase skip localizes to the endoplasmic reticulum and translocates to membrane ruffles following.... J Biol Chem. 2003; 278(13):11376-85. DOI: 10.1074/jbc.M209991200. View

16.

Bouzakri K, Roques M, Gual P, Espinosa S, Guebre-Egziabher F, Riou J . Reduced activation of phosphatidylinositol-3 kinase and increased serine 636 phosphorylation of insulin receptor substrate-1 in primary culture of skeletal muscle cells from patients with type 2 diabetes. Diabetes. 2003; 52(6):1319-25. DOI: 10.2337/diabetes.52.6.1319. View

17.

Iwawaki T, Akai R, Kohno K, Miura M . A transgenic mouse model for monitoring endoplasmic reticulum stress. Nat Med. 2004; 10(1):98-102. DOI: 10.1038/nm970. View

18.

Sarbassov D, Ali S, Kim D, Guertin D, Latek R, Erdjument-Bromage H . Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol. 2004; 14(14):1296-302. DOI: 10.1016/j.cub.2004.06.054. View

19.

Ozcan U, Cao Q, Yilmaz E, Lee A, Iwakoshi N, Ozdelen E . Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004; 306(5695):457-61. DOI: 10.1126/science.1103160. View

20.

Lillioja S, Mott D, Howard B, BENNETT P, Yki-Jarvinen H, Freymond D . Impaired glucose tolerance as a disorder of insulin action. Longitudinal and cross-sectional studies in Pima Indians. N Engl J Med. 1988; 318(19):1217-25. DOI: 10.1056/NEJM198805123181901. View