title: AMPK activation by prolonged stimulation with interleukin-1β contributes to the promotion of GLUT4 translocation in skeletal muscle cells.
abstract: Impaired insulin signaling in skeletal muscle cells causes insulin resistance associated with the onset of type 2 diabetes. Although interleukin (IL)-1β has been considered to be implicated in the pathogenesis of type 2 diabetes, the action of prolonged stimulation with IL-1β on the insulin signaling pathway in skeletal muscle cells remains poorly understood. In the current study, we investigated the effect of IL-1β stimulation on insulin signal transduction from the insulin receptor (IR), resulting in glucose transporter 4 (GLUT4) translocation in skeletal muscle cells. In L6-GLUT4myc cells, stimulation with IL-1β for 24 h promoted GLUT4 translocation to the plasma membrane and increased glucose uptake in a concentration-dependent manner, whereas short-term stimulation with IL-1 for up to 6 h did not affect that. In addition, stimulation with IL-1β for 24 h further increased insulin-stimulated GLUT4 translocation. Interestingly, stimulation with IL-1β for 24 h did not cause any change in the phosphorylation of insulin signal molecules IR, insulin receptor substrate (IRS)-1, Akt, and p21-activated kinase (PAK1). Stimulation with IL-1β for 24 h significantly increased AMP-activated protein kinase (AMPK) phosphorylation and GLUT4 protein expression. Small interfering RNA (siRNA) targeting AMPK1/2 significantly inhibited IL-1β-stimulated GLUT4 translocation. These results suggest that prolonged stimulation with IL-1β positively regulates GLUT4 translocation in skeletal muscle cells. IL-1β may have a beneficial effect on maintaining glucose homeostasis in skeletal muscle cells in patients with type 2 diabetes. .
authors: Department of Pharmacology, Hokkaido Pharmaceutical University School of Pharmacy, 7-15-4-1 Maeda, Teine-ku, Sapporo, 006-8590, Japan.
authors: Akira
authors: A
authors: Takaguri
authors: Department of Pharmacology, Hokkaido Pharmaceutical University School of Pharmacy, 7-15-4-1 Maeda, Teine-ku, Sapporo, 006-8590, Japan.
authors: Saya
authors: S
authors: Inoue
authors: Department of Pharmacology, Hokkaido Pharmaceutical University School of Pharmacy, 7-15-4-1 Maeda, Teine-ku, Sapporo, 006-8590, Japan.
authors: Takashi
authors: T
authors: Kubo
authors: Department of Pharmacology, Hokkaido Pharmaceutical University School of Pharmacy, 7-15-4-1 Maeda, Teine-ku, Sapporo, 006-8590, Japan. kumi@hokuyakudai.ac.jp.
authors: Kumi
authors: K
authors: Satoh
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D034741:RNA, Small Interfering; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D053583:Interleukin-1beta; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C495694:Slc2a4 protein, rat; D011972:Receptor, Insulin; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: AMPK; GLUT4; insulin signaling; interleukin-1; skeletal muscle cells