Human Muscle Fiber Type-Specific Insulin Signaling: Impact of Obesity and Type 2 Diabetes

摘要

Skeletal muscle is a heterogeneous tissue composed of different fiber types. Studies suggest that insulin-mediated glucose metabolism is different between muscle fiber types. We hypothesized that differences are due to fiber type-specific expression/regulation of insulin signaling elements and/or metabolic enzymes. Pools of type Ⅰ and Ⅱ fibers were prepared from biopsies of the vastus lateralis muscles from lean, obese, and type 2 diabetic subjects before and after a hyperinsulinemic-euglycemic clamp. Type Ⅰ fibers compared with type Ⅱ fibers have higher protein levels of the insulin receptor, GLUT4, hexokinase Ⅱ, glycogen synthase (GS), and pyru-vate dehydrogenase-E1α (PDH-E1α) and a lower protein content of Akt2, TBC1 domain family member 4 (TBC1D4), and TBC1D1. In type Ⅰ fibers compared with type Ⅱ fibers, the phosphorylation response to insulin was similar (TBC1D4, TBC1D1, and GS) or decreased (Akt and PDH-E1α). Phosphorylation responses to insulin adjusted for protein level were not different between fiber types. Independently of fiber type, insulin signaling was similar (TBC1D1, GS, and PDH-E1α) or decreased (Akt and TBC1D4) in muscle from patients with type 2 diabetes compared with lean and obese subjects. We conclude that human type Ⅰ muscle fibers compared with type Ⅱ fibers have a higher glucose-handling capacity but a similar sensitivity for phosphoregulation by insulin.