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DGAT1 inhibitors protect pancreatic β-cells from palmitic acid-induced apoptosis

  
@article{APS10271,
	author = {Jun-shang Huang and Bin-bin Guo and Gai-hong Wang and Li-min Zeng and You-hong Hu and Ting Wang and He-yao Wang},
	title = {DGAT1 inhibitors protect pancreatic β-cells from palmitic acid-induced apoptosis},
	journal = {Acta Pharmacologica Sinica},
	volume = {42},
	number = {2},
	year = {2021},
	keywords = {},
	abstract = {Previous studies demonstrated that prolonged exposure to elevated levels of free fatty acids (FFA), especially saturated fatty acids, could lead to pancreatic β-cell apoptosis, which plays an important role in the progression of type 2 diabetes (T2D). Diacylglycerol acyltransferase 1 (DGAT1), an enzyme that catalyzes the final step of triglyceride (TG) synthesis, has been reported as a novel target for the treatment of multiple metabolic diseases. In this study we evaluated the potential beneficial effects of DGAT1 inhibitors on pancreatic β-cells, and further verified their antidiabetic effects in db/db mice. We showed that DGAT1 inhibitors (4a and LCQ908) at the concentration of 1 μM significantly ameliorated palmitic acid (PA)-induced apoptosis in MIN6 pancreatic β-cells and primary cultured mouse islets; oral administration of a DGAT1 inhibitor (4a) (100 mg/kg) for 4 weeks significantly reduced the apoptosis of pancreatic islets in db/db mice. Meanwhile, 4a administration significantly decreased fasting blood glucose and TG levels, and improved glucose tolerance and insulin tolerance in db/db mice. Furthermore, we revealed that pretreatment with 4a (1 μM) significantly alleviated PA-induced intracellular lipid accumulation, endoplasmic reticulum (ER) stress, and proinflammatory responses in MIN6 cells, which might contribute to the protective effects of DGAT1 inhibitors on pancreatic β-cells. These findings provided a better understanding of the antidiabetic effects of DGAT1 inhibitors.},
	url = {http://www.chinaphar.com/article/view/10271}
}