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

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.