Heat treatment reduced the expression of miR-7-5p to facilitate insulin-stimulated lactate secretion by targeting IRS2 in boar Sertoli cells.

Insulin dysfunction of diabetes mellitus (DM) disorders the glucose metabolism in Sertoli cells (SCs), resulting in the impairment of spermatogenesis.Insulin signaling system in Sertoli cells (SCs) plays an important role in regulating lactate secretion. Heat treatment could increase the lactate secretion of boar SCs, but whether heat treatment participates in lactate secretion by improving the sensitivity of insulin is unknown. In the current study, the primary SCs from 21-day-old boar were employed to treat with 100 nM insulin for 24 h or heat treatment (43 °C, 30 min). Heat treatment strengthened the effect of insulin on the effect of lactate secretion. In addition, heat treatment increased the expression of insulin-induced insulin receptor substrate 2 (IRS2), but reduced the expression of miR-7-5p. Using dual luciferase reporter assay and Western blot, the study found that IRS2 is a potential target gene of miR-7-5p. Heat treatment also enhanced the Phosphorylation of insulin-stimulated PI3K/Akt, and increased lactate secretion by promoting the expression of Glucose Transporter 3 (GLUT3), Lactate Dehydrogenase-A (LDHA) and monocarboxylate transporter 1 (MCT1). Furthermore, miR-7-5p inhibitor could partly mimic the effects of heat treatment on lactate production of SCs, indicating that heat treatment improves insulin sensitivity by regulating the expression of miR-7-5p/IRS2/PI3K/Akt. These results reveal a novel miRNA-mediated mechanism of heat treatment on the regulation of lactate metabolism production, and suggest that targeting miR-7-5p is a probably therapeutic method to insulin dysfunction-induced metabolic diseases.