Apolipoprotein A-I enhances insulin-dependent and insulin-independent glucose uptake by skeletal muscle

• Published in: Scientific reports Vol. 9; no. 1; p. 1350
• Main Authors: Tang, Shudi, Tabet, Fatiha, Cochran, Blake J., Cuesta Torres, Luisa F., Wu, Ben J., Barter, Philip J., Rye, Kerry-Anne
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.02.2019; Nature Publishing Group
• Subjects: 1-Phosphatidylinositol 3-kinase; 13/106; 13/109; 38/77; 631/80/304; 692/163/2743/137/773; ABCA1 protein; AKT protein; Apolipoprotein A; Apolipoprotein A-I; Apolipoproteins; ATP-binding protein; Cell surface; Diabetes mellitus (insulin dependent); Diabetes mellitus (non-insulin dependent); Glucose; Glucose transporter; High density lipoprotein; Humanities and Social Sciences; Insulin; Insulin receptor substrate 1; Insulin resistance; multidisciplinary; Musculoskeletal system; Phosphatidylinositol 4,5-diphosphate; Phosphorylation; Protein-serine/threonine kinase; Scavenger receptors; Science; Science (multidisciplinary); Signal transduction; Skeletal muscle; Therapeutic applications
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-38014-3

Therapeutic interventions that increase plasma high density lipoprotein (HDL) and apolipoprotein (apo) A-I levels have been reported to reduce plasma glucose levels and attenuate insulin resistance. The present study asks if this is a direct effect of increased glucose uptake by skeletal muscle. Incubation of primary human skeletal muscle cells (HSKMCs) with apoA-I increased insulin-dependent and insulin–independent glucose uptake in a time- and concentration-dependent manner. The increased glucose uptake was accompanied by enhanced phosphorylation of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), the serine/threonine kinase Akt and Akt substrate of 160 kDa (AS160). Cell surface levels of the glucose transporter type 4, GLUT4, were also increased. The apoA-I-mediated increase in glucose uptake by HSKMCs was dependent on phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt, the ATP binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-B1). Taken together, these results establish that apoA-I increases glucose disposal in skeletal muscle by activating the IR/IRS-1/PI3K/Akt/AS160 signal transduction pathway. The findings suggest that therapeutic agents that increase apoA-I levels may improve glycemic control in people with type 2 diabetes.