PMID:23357280

Citation	Macdonald, MJ, Hasan, NM, Dobrzyn, A, Stoker, SW, Ntambi, JM, Liu, X and Sampath, H (2013) Knockdown of pyruvate carboxylase or fatty acid synthase lowers numerous lipids and glucose-stimulated insulin release in insulinoma cells. Arch. Biochem. Biophys. 532:23-31
Abstract	We previously showed that knockdown of the anaplerotic enzyme pyruvate carboxylase in the INS-1 832/13 insulinoma cell line inhibited glucose-stimulated insulin release and glucose carbon incorporation into lipids. We now show that knockdown of fatty acid synthase (FAS) mRNA and protein also inhibits glucose-stimulated insulin release in this cell line. Levels of numerous phospholipids, cholesterol esters, diacylglycerol, triglycerides and individual fatty acids with C(14)-C(24) side chains were acutely lowered about 20% in glucose-stimulated pyruvate carboxylase knockdown cells over a time course that coincides with insulin secretion. In FAS knockdown cells glucose carbon incorporation into lipids and the levels of the subclasses of phospholipids and cholesterol ester species were lower by 20-30% without inhibition of glucose oxidation. These studies suggest that rapid lipid modification is essential for normal glucose-stimulated insulin secretion.
Links	PubMed Online version:10.1016/j.abb.2013.01.002
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:PYC		GO:0071073: positive regulation of phospholipid biosynthetic process	ECO:0000315:		P		Fig. 2. Lower levels of many individual and total phospholipids in glucose-stimulated INS-1 832/13-derived cell lines with knocked down pyruvate carboxylase.	complete CACAO 6618
RAT:PYC	involved_in	GO:0071073: positive regulation of phospholipid biosynthetic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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