A J Meijer

..Amino acid-dependent signal transduction is present in all insulin-sensitive tissues and in pancreatic beta cells. A defect in amino acid-dependent signal transduction may result in phenomena similar to those found in diabetes mellitus...

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..Unfortunately, unawareness of possible metabolic complications may sometimes lead to misinterpretation of the data obtained...

..2008) provide evidence that basal autophagy is necessary to maintain the architecture and function of pancreatic beta cells and that its induction in diabetic mice protects beta cells against damage by oxidative stress...

..We discuss the possibility that this may be a useful mechanism for eliminating damaged mitochondria and other cell structures to prevent cell death...

..The data suggest that in mammalian cells, as in yeast, AMPK is required for autophagy...

..Autophagy is controlled by complex signalling pathways, including that used by insulin. In these pathways, phosphatidylinositol 3-kinases and the protein kinase mTOR play important roles...

..Two recent studies have shed light on the molecular mechanism by which AMPK controls autophagic flux...

..Finally, amino acid-dependent signalling controls the production of leptin by adipocytes, and thus contributes to the regulation of appetite...

..Amino acid-dependent signaling also promotes insulin production by beta-cells. This further adds to the anabolic properties of amino acids. It is concluded that amino acids are important regulators of major metabolic pathways...

..In contrast, dietary carbohydrate content affects the postabsorptive rate of gluconeogenesis minimally, as evidenced by only a slight increase in gluconeogenesis during severe carbohydrate restriction...

..A high dietary fat intake is involved in the pathogenesis of insulin resistance...

..Variation in glucose 6-phosphate does not always result in activity changes of GSa. Activation of glucose 6-phosphatase flux by fatty acids may contribute to the increased hepatic glucose production as seen in Type 2 diabetes...

..Increased plasma free fatty acid (FFA) concentrations may be in part responsible for the increased levels of ceramide in skeletal muscle of obese subjects...

..By deduction, dietary carbohydrate is required for an optimal regulation of absorptive, rather than postabsorptive, protein metabolism...

..Mitochondria did not show uncoupling. CONCLUSIONS: Clofibrate does not improve glucose tolerance by improving hepatic glucose or glycogen metabolism. Peripheral glucose oxidation may be facilitated by increased energy dissipation...

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..01 compared with the other diets). A euenergetic high-fat diet results in increased postabsorptive FFA release and fat oxidation, whereas a euenergetic high-carbohydrate diet does not affect these variables of fat metabolism...

..Thiazolidinediones increase peripheral insulin sensitivity and decrease plasma free fatty acids (FFA). However, their exact mechanism of action has not been fully elucidated...

..Association of HK with mitochondria may promote inhibition of the mitochondrial permeability transition pore and thereby reduce cell death and apoptosis...

..Dietary fat content influences bile salt metabolism, but quantitative data from controlled studies in humans are scarce...

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..Protein synthesis is strongly inhibited when AMPK is activated. It is concluded that amino acid-dependent signaling, a protein-anabolic signal, can be effectively antagonized by activation of AMPK...

..The aim of this study was to investigate the type of flush solution, temperature and anticoagulant content on the wash-out of the non-heart-beating donor (NHBD) rat liver...

..The mechanism by which amino acids stimulate mTORdependent signaling (and other signaling pathways), and its molecular connection with the autophagic machinery, is still unknown...

..It is concluded that the decrease in cell volume, following the breakdown of sphingomyelin in the plasma membrane of the hepatocyte, may contribute to the abnormal metabolism of glucose when TNF-alpha levels are high...

..In conclusion, adiponectin production is substrate driven. Phosphatidylinositol 3-kinase and an acidic lysosomal pH, but not amino acid-mediated mTOR signaling or lysosomal breakdown, are involved in adiponectin secretion...

..In conclusion, preservation of the NHBD rat liver by hypothermic MP is superior to CS. Furthermore, MP using Polysol results in better-quality liver preservation compared with using UW-G...

..The aim of the present review is to give an overview of autophagy and to discuss its regulation by activators and effectors of mTOR and GTPases...

..These results suggest that the inhibition of autophagy by AICAR is not related to its ability to activate AMPK. We conclude that in mammalian cells, as in yeast, AMPK is required for autophagy...