ReferenceID 1507
Chronic Exposure to Palmitic Acid Down-Regulates AKT in Beta-Cells through Activation of mTOR
Am J Pathol
High circulating lipids occurring in obese individuals and insulin-resistant patients are considered a contributing factor to type 2 diabetes. Exposure to high lipid concentration is proposed to both protect and damage b
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Record Fields
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- Reference Id
- 1507
- Evidence Id
- 18097
- Core Evidence Id
- 18097
- Source Reference Id
- 3021
- Herb2 Reference Id
- HBREF003818
- Subject Paper Key
- HBIN020174_34619135
- Pubmed Id
- 34619135
- Doi
- 10.1016/j.ajpath.2021.09.008
- Paper Title
- Chronic Exposure to Palmitic Acid Down-Regulates AKT in Beta-Cells through Activation of mTOR
- Paper Abstract
- High circulating lipids occurring in obese individuals and insulin-resistant patients are considered a contributing factor to type 2 diabetes. Exposure to high lipid concentration is proposed to both protect and damage beta-cells under different circumstances. Here, by feeding mice a high-fat diet (HFD) for 2 weeks to up to 14 months, the study showed that HFD initially causes the beta-cells to expand in population, whereas long-term exposure to HFD is associated with failure of beta-cells and the inability of animals to respond to glucose challenge. To prevent the failure of beta-cells and the development of type 2 diabetes, the molecular mechanisms that underlie this biphasic response of beta-cells to lipid exposure were explored. Using palmitic acid (PA) in cultured beta-cells and islets, the study demonstrated that chronic exposure to lipids leads to reduced viability and inhibition of cell cycle progression concurrent with down-regulation of a pro-growth/survival kinase AKT, independent of glucose. This AKT down-regulation by PA is correlated with the induction of mTOR/S6K activity. Inhibiting mTOR activity with rapamycin induced Raptor and restored AKT activity, allowing beta-cells to gain proliferation capacity that was lost after HFD exposure. In summary, a novel mechanism in which lipid exposure may cause the dipole effects on beta-cell growth was elucidated, where mTOR acts as a lipid sensor. These mechanisms can be novel targets for future therapeutic developments.
- Journal
- Am J Pathol
- Publish Year
- 2021
- Experiment Subject
- mouse; patient; cultured beta-cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Type 2 Diabetes; Obese; Insulin-resistant
- Paper Title Cn
- Paper Title En
- Chronic Exposure to Palmitic Acid Down-Regulates AKT in Beta-Cells through Activation of mTOR
- Bilingual Status
- semi_complete