Research Bio
Plasma lipoproteins are the major vehicles for non-aqueous transport of lipids, including cholesterol and triglyceride, and lipid-soluble vitamins such as vitamin A and E, from the liver and intestine to tissues. Derangements in lipoprotein metabolism are involved in progression of atherosclerosis, an underlying cause of heart disease and strokes which remain the major cause of death in the United States. Insulin, known as a key regulator in carbohydrate metabolism, plays a major regulatory role in hepatic lipoprotein metabolism. Insulin acts by inhibition of secretion of triglyceride-rich lipoproteins through a mechanism involving the stimulation of the intracellular degradation of apolipoprotein B, an essential structural apolipoprotein.
Research in my laboratory links specific events involved in insulin receptor (IR) signal transduction with microsomal events that lead to degradation of apo B. The focus is on insulin-activated phosphatidylinositide 3-kinase (PI-3-kinase) in the translocation of apo B and its intracellular transport within the secretory pathway. Investigations employ primary rat hepatocytes, McArdle RH-7777 rat hepatoma cells and HepG2 cells and assay of IR signaling, Beta-subunit phosphorylation, IRS phosphorylation, PI 3-K activation and of PI 3-K mass in subcellular fractions. Progress will allow better understanding of insulin regulation of triglyceride-rich lipoprotein secretion by liver and will provide insights into the mechanisms involved in the development of hypertriglyceridemia in human obesity and insulin resistance syndromes such as metabolic Syndrome X which increase the risk of atherosclerosis complications up to ten times.
2011 May
Kim E, Liu NC, Yu IC, Lin HY, Lee YF, Sparks JD, Chen LM, Chang C. "Metformin inhibits nuclear receptor TR4-mediated hepatic stearoyl-CoA desaturase 1 gene expression with altered insulin sensitivity." Diabetes. 2011 May 0; 60(5):1493-503. Epub 2011 Apr 08. |
2011 Mar 11
Sparks JD, Chamberlain J, O'Dell C, Khatun I, Hussain MM, Sparks CE. "Acute suppression of apo B secretion by insulin occurs independently of MTP." Biochemical and biophysical research communications. 2011 Mar 11; 406(2):252-6. Epub 2011 Feb 18. |
2011 Jan 17
Nigro P, Satoh K, O'Dell MR, Soe NN, Cui Z, Mohan A, Abe JI, Alexis JD, Sparks JD, Berk BC. "Cyclophilin A is an inflammatory mediator that promotes atherosclerosis in apolipoprotein E-deficient mice." The Journal of experimental medicine. 2011 Jan 17; 208(1):53-66. Epub 2010 Dec 20. |
2010 Nov
Galloway CA, Ashton J, Sparks JD, Mooney RA, Smith HC. "Metabolic regulation of APOBEC-1 complementation factor trafficking in mouse models of obesity and its positive correlation with the expression of ApoB protein in hepatocytes." Biochimica et biophysica acta. 2010 Nov 0; 1802(11):976-85. Epub 2010 Jun 09. |
2010 Oct
Sparks JD, Cianci J, Jokinen J, Chen LS, Sparks CE. "Interleukin-6 mediates hepatic hypersecretion of apolipoprotein B." American journal of physiology. Gastrointestinal and liver
physiology. 2010 Oct 0; 299(4):G980-9. Epub 2010 Jul 22. |
