............................................................................................................................ xi CHAPTER 1. GENERAL INTRODUCTION ......................................................................... 1 Thesis Organization ............................................................................................................. 1 Literature Review ..............

Palmitate overload induces hepatic cell dysfunction characterized by enhanced apoptosis and altered citric acid cycle (CAC) metabolism; however, the mechanism of how this occurs is incompletely understood. We hypothesize that elevated doses of palmitate disrupt intracellular calcium homeostasis resulting in a net flux of calcium from the ER to mitochondria, activating aberrant oxidative metabol...

We investigated the effects of Astragalus polysaccharide (APS) on palmitate-induced insulin resistance in C2C12 skeletal muscle myotubes. Palmitate-reduced glucose uptake was restored by APS. APS prevented palmitate-induced C2C12 myotubes from impaired insulin signaling by inhibiting Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1) and increasing Ser473 phosphorylation of Akt. Mor...

Endoplasmic reticulum (ER) stress and autophagy have both been reported to be associated with lipotoxicity in β-cells, yet the relationship between them has not been fully clarified. In the present study, we tested the hypothesis that the ER stress-autophagic pathway in β-cells is a downstream pathway activated following saturated fatty acid treatment. Mouse insulinoma (MIN6) β-cells were treat...

Abstract Type I diabetes mellitus is an autoimmune disease characterized by the destruction of β-cells, leading to severe insulin deficiency. Environmental factors and genetic predisposition are implicated in β-cell destruction, which final step a cascade complex events. Possible triggers activation Fas, perforin, increased generation reactive oxygen species, production inflammatory cytokines, ...

The mechanism by which fatty acids stimulate the biosynthesis of phosphatidylcholine has been studied in cultured rat hepatocytes. Long chain fatty acids (1 mM) stimulated approximately 1.9-fold [methyl-3H] choline incorporation from phosphocholine into phosphatidylcholine by isolated hepatocytes. Oleate and palmitate (4 mM) enhanced phosphatidylcholine production by 3- and 2.2-fold, respective...

Lipoapoptosis occurring due to an excess of saturated free fatty acids such as palmitate is a key pathogenic event in the initiation of nonalcoholic fatty liver disease. Palmitate loading of cells activates the endoplasmic reticulum stress response, including induction of the proapoptotic transcription factor C/EBP homologous protein (CHOP). Furthermore, the loss of microRNAs is implicated in r...

In this study isolated perfused working rat hearts were used to investigate the role of palmitate-regulated protein kinase B (PKB) phosphorylation on glucose metabolism. Rat hearts were perfused aerobically in working mode with 11 mM glucose and either 100 microU/ml insulin or 100 microU/ml insulin and 1.2 mM palmitate. PKB activity and phosphorylation state were reduced in the presence of 1.2 ...

Plasma free fatty acid (FFA) kinetics in humans are often measured with only one tracer. In study 1, healthy volunteers received infusions of [U-¹³C]linoleate, [U-¹³C]oleate, and [U-¹³C]palmitate during continuous feeding with liquid meals low (n = 12) and high (n = 5) in palmitate and containing three labeled fatty acids to measure FFA appearance and fractional spillover of lipoprotein lipase-...

New chemical kinetic reaction mechanisms are developed for two of the five major components of biodiesel fuel, methyl stearate and methyl oleate. The mechanisms are produced using existing reaction classes and rules for reaction rates, with additional reaction classes to describe other reactions unique to methyl ester species. Mechanism capabilities were examined by computing fuel/air autoignit...