AI Article Synopsis
- AMPK activation enhances glucose and lipid metabolism, and the ADAM17 inhibitor SN-4 is found to activate AMPK, leading to increased GLUT4 translocation and sugar uptake.
- The AMPK inhibitor dorsomorphin reversed the effects of SN-4, confirming that the benefits come from AMPK activation.
- SN-4 also reduces lipid accumulation in liver cells and inhibits TNF-α release, highlighting its potential as a new antidiabetic drug that manages blood sugar and prevents complications without significant side effects like lactic acidosis.
Article Abstract
AMPK activation promotes glucose and lipid metabolism. Here, we found that our previously reported ADAM17 inhibitor SN-4 activates AMPK and promotes membrane translocation and sugar uptake of GLUT4. AMPK inhibitor dorsomorphin reversed this effect of SN-4, confirming that the effect is mediated by AMPK activation. In addition, SN-4 inhibited lipid accumulation in HepG2 under high glucose conditions by promoting lipid metabolism and inhibiting lipid synthesis. Although lactic acidosis is a serious side effect of biguanides such as metformin, SN-4 did not affect lactate production. Furthermore, SN-4 was confirmed to inhibit the release of TNF-α, a causative agent of insulin resistance, from adipocytes. In diabetes treatment, it is important to not only regulate blood sugar levels but also prevent complications. Our findings reveal the therapeutic potential of SN-4 as a new antidiabetic drug that can also help prevent future complications.
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| http://dx.doi.org/10.1016/j.jphs.2023.11.005 | DOI Listing |
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