A high sucrose and high fat diet induced the development of insulin resistance in the skeletal muscle of Bama miniature pigs through the Akt/GLUT4 pathway

摘要

A high sucrose and high fat (HSHF) diet induces insulin resistance (IR) and increased susceptibility to type 2 diabetes mellitus (T2DM), but the underlying mechanisms are poorly characterized. This study aimed to investigate the molecular mechanisms by which the HSHF diet impairs insulin sensitivity in Bama miniature pigs ( sus scrofa domesticus ). Twelve Bama miniature pigs were randomly assigned to the control diet (CD) group (n=6) or the HSHF group (n=6) for 6 months. Biochemical parameters were measured. Western blot, RT-qPCR and immunohistochemistry were used to profile the changes of protein expression, mRNA expression and glucose transporter 4 (GLUT4) expression in skeletal muscle tissues, respectively. In comparison to the CD group, the homeostasis model assessment-insulin resistance (HOMA-IR) index of the HSHF group demonstrated a 2.9-fold increase, and the insulin sensitivity showed a 24.8% decrease. Compared with the CD group, p-Akt S473 decreased by approximately 59% and GLUT4 decreased by 43.8% in the skeletal muscle of the HSHF group. However, the expression of p-mTOR S2448 between the 2 groups was not significantly different ( P =0.309). This study demonstrates that a 6-month HSHF diet caused IR, decreased insulin sensitivity, and reduced the expression of p-Akt S473 and GLUT4 in the skeletal muscle of Bama miniature pigs.