Chronic Exposure to Palmitic Acid Downregulates AKT in Beta-Cells through Activation of mTOR
Aggarwal, R.; Peng, Z.; Zeng, N.; Silva, J.; He, L.; Chen, J.; Debebe, A.; Stiles, E.; Chen, C.-Y.; Stiles, B. L.
Show abstract
High circulating lipids occurring in obese individuals and insulin resistant patients are considered a contributing factor to Type 2 Diabetes (T2D). Exposure to high lipids initially causes the beta-cells to expand in population. Long-term exposure to high lipids however is associated with failure of beta-cells and the development of T2D. To prevent the failure of beta-cells and development of Type 2 Diabetes, this study focuses on understanding the molecular mechanisms that underlie this biphasic response of beta-cells to lipid exposure. Using palmitic acid (PA) in cultured beta-cells and islets, we demonstrated that chronic exposure to lipids leads to reduced viability and inhibition of cell cycle progression concurrent with downregulation of a pro-growth/survival kinase AKT, independent of glucose. This AKT downregulation by PA treatment is correlated with a consistent induction of mTOR/S6K activity concurrent with AKT downregulation. Inhibiting mTOR activity restores AKT activity and allows beta-cells to gain proliferation capacity that are lost after high fat diet exposure. In summary, we elucidated a novel mechanism for which lipid exposure may cause the dipole effects on beta-cell growth, where mTOR acts as a lipid sensor. These mechanisms can be novel targets for future therapeutic developments.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Glucagon Receptor Signaling at White Adipose Tissue Does Not Regulate Lipolysis 96%
- Caloric Restriction recovers impaired β-cell-β-cell coupling, calcium oscillation coordination and insulin secretion in prediabetic mice 96%
- Adipose depot-specific upregulation of Ucp1 or mitochondrial oxidative complex proteins are early consequences of genetic insulin reduction in mice 96%
Similar papers in this journal
- Human adipocyte differentiation and composition of disease relevant lipids are regulated by miR-221-3p 93%
- A diet-independent zebrafish model for NAFLD recapitulates patient lipid profiles and offers a system for small molecule screening 93%
- ABCA1 deficiency causes tissue-specific dysregulation of the SREBP2 pathway in mice 93%
Similar papers in this journal
- The leptin receptor has no role in delta-cell control of beta-cell function in the mouse 95%
- Spinal Cord Injury Reduces Serum Levels of Fibroblast Growth Factor-21 and Impairs its Signaling Pathways in Liver and Adipose Tissue in Mice 95%
- The Novel Chimeric Multi-Agonist Peptide (GEP44) Reduces Energy Intake and Body Weight in Male and Female Diet-Induced Obese Mice in a Glucagon-Like Peptide-1 Receptor-Dependent Manner 94%
Similar papers in this journal
- Bax and Bak jointly control survival and dampen the early unfolded protein response in pancreatic β-cells under glucolipotoxic stress 96%
- G-Protein Coupled Receptor 19 (Gpr19) Knockout Mice Display Sex-Dependent Metabolic Dysfunction 95%
- Fenretinide inhibits obesity and fatty liver disease but induces Smpd3 to increase serum ceramides and worsen atherosclerosis in LDLR-/- mice. 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.