Trilobatin ameliorates insulin resistance through IRS-AKT-GLUT4 signaling pathway in C2C12 myotubes and ob/ob mice
Background: Trilobatin, a natural compound, has been found to exhibit anti-diabetic properties in high-fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic mice. But up to now no research has been reported on the effect of trilobatin on insulin resistance in peripheral tissues. Herein, we determined the effects of trilobatin on insulin resistance in palmitate-treated C2C12 myotubes and ob/ob mice.
Methods: 8-10 weeks of male ob/ob mice and same background C57BL/6 mice were used to evaluate the role of trilobatin on insulin resistance; Protein expression and phosphorylation were measured by western blot; Glucose uptake was determined a fluorescent test.
Results: treatment with trilobatin prevented palmitate-induced insulin resistance by enhancing glucose uptake and the phosphorylation of insulin resistance substrate 1 (IRS1) and protein Kinase B, (PKB/AKT), recovered the translocation of GLUT4 from cytoplasm to membrane, but preincubation with LY294002, an inhibitor of PI3K, blocked the effects of trilobatin on glucose uptake and the distribution of GLUT4 in C2C12 myotubes. Furthermore, administration with trilobatin for 4 weeks significantly improved insulin resistance by decreasing fasting blood glucose and insulin in serum, enhancing the phosphorylation of IRS1 and AKT, and recovering the expression and translocation of GLUT4 in ob/ob mice.
Conclusions: IRS-AKT-GLUT4 signaling pathway might be involved in trilobatin ameliorating insulin resistance in skeletal muscle of obese animal models.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
This is a list of supplementary files associated with this preprint. Click to download.
Posted 16 Sep, 2020
On 12 Oct, 2020
On 01 Oct, 2020
Received 27 Sep, 2020
On 21 Sep, 2020
Invitations sent on 18 Sep, 2020
On 15 Sep, 2020
On 14 Sep, 2020
On 14 Sep, 2020
On 04 Sep, 2020
Received 03 Sep, 2020
Received 29 Aug, 2020
On 25 Aug, 2020
On 24 Aug, 2020
Invitations sent on 10 Aug, 2020
On 24 Jul, 2020
On 23 Jul, 2020
On 23 Jul, 2020
On 22 Jul, 2020
Trilobatin ameliorates insulin resistance through IRS-AKT-GLUT4 signaling pathway in C2C12 myotubes and ob/ob mice
Posted 16 Sep, 2020
On 12 Oct, 2020
On 01 Oct, 2020
Received 27 Sep, 2020
On 21 Sep, 2020
Invitations sent on 18 Sep, 2020
On 15 Sep, 2020
On 14 Sep, 2020
On 14 Sep, 2020
On 04 Sep, 2020
Received 03 Sep, 2020
Received 29 Aug, 2020
On 25 Aug, 2020
On 24 Aug, 2020
Invitations sent on 10 Aug, 2020
On 24 Jul, 2020
On 23 Jul, 2020
On 23 Jul, 2020
On 22 Jul, 2020
Background: Trilobatin, a natural compound, has been found to exhibit anti-diabetic properties in high-fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic mice. But up to now no research has been reported on the effect of trilobatin on insulin resistance in peripheral tissues. Herein, we determined the effects of trilobatin on insulin resistance in palmitate-treated C2C12 myotubes and ob/ob mice.
Methods: 8-10 weeks of male ob/ob mice and same background C57BL/6 mice were used to evaluate the role of trilobatin on insulin resistance; Protein expression and phosphorylation were measured by western blot; Glucose uptake was determined a fluorescent test.
Results: treatment with trilobatin prevented palmitate-induced insulin resistance by enhancing glucose uptake and the phosphorylation of insulin resistance substrate 1 (IRS1) and protein Kinase B, (PKB/AKT), recovered the translocation of GLUT4 from cytoplasm to membrane, but preincubation with LY294002, an inhibitor of PI3K, blocked the effects of trilobatin on glucose uptake and the distribution of GLUT4 in C2C12 myotubes. Furthermore, administration with trilobatin for 4 weeks significantly improved insulin resistance by decreasing fasting blood glucose and insulin in serum, enhancing the phosphorylation of IRS1 and AKT, and recovering the expression and translocation of GLUT4 in ob/ob mice.
Conclusions: IRS-AKT-GLUT4 signaling pathway might be involved in trilobatin ameliorating insulin resistance in skeletal muscle of obese animal models.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9