Gh , Igf - I and Insulin in the Regulation of Lipid and Lipoprotein Metabolism Fredrik Frick Göteborg 2001
نویسندگان
چکیده
.......................................................................................................................................................... 3 CONTENTS........................................................................................................................................................... 4 LIST OF PUBLICATIONS.................................................................................................................................. 6 LIST OF ABBREVIATIONS............................................................................................................................... 7 INTRODUCTION................................................................................................................................................. 9 GENERAL INTRODUCTION .................................................................................................................................... 9 GROWTH HORMONE ............................................................................................................................................. 9 Effects of GH................................................................................................................................................. 10 INSULIN ............................................................................................................................................................. 10 Effects of insulin............................................................................................................................................ 11 INSULIN RESISTANCE ......................................................................................................................................... 11 Free fatty acids and insulin resistance.......................................................................................................... 12 The glucose fatty acid cycle .......................................................................................................................... 12 GH and insulin resistance............................................................................................................................. 13 INSULIN-LIKE GROWTH FACTOR-I ...................................................................................................................... 14 Effects of IGF-I ............................................................................................................................................. 14 Insulin-like growth factor binding proteins (IGFBPs).................................................................................. 15 LIPOPROTEIN METABOLISM................................................................................................................................ 15 APOLIPOPROTEIN B AND APOB MRNA EDITING................................................................................................ 18 HORMONAL REGULATION OF LIPOPROTEIN METABOLISM .................................................................................. 19 GH in man..................................................................................................................................................... 19 GH in experimental animals ......................................................................................................................... 20 Insulin ........................................................................................................................................................... 20 LIPOPROTEIN LIPASE.......................................................................................................................................... 21 Synthesis and transport of LPL ..................................................................................................................... 22 Hormonal regulation of LPL activity ............................................................................................................ 23 LIPOGENESIS AND LIPOLYSIS ............................................................................................................................. 23 Lipogenesis ................................................................................................................................................... 24 Lipoplysis and hormone-sensitive lipase (HSL) ............................................................................................ 24 AIMS OF THE STUDIES ................................................................................................................ 27 METHODOLOGICAL CONSIDERATIONS ................................................................................................. 28 ANIMAL MODELS ............................................................................................................................................... 28 Hypophysectomised female rats .................................................................................................................... 28 Hormonal treatment ...................................................................................................................................... 28 Cortisol and thyroxine................................................................................................................................................. 28 Growth hormone ......................................................................................................................................................... 28 Insulin-like growth factor-I ......................................................................................................................................... 29 Insulin ......................................................................................................................................................................... 29 Bovine growth hormone transgenic mice...................................................................................................... 30 SIZE EXCLUSION CHROMATOGRAPHY OF SERUM LIPOPROTEINS......................................................................... 30 HEPATIC TRIGLYCERIDE SECRETION IN VIVO ..................................................................................................... 31 GLUCOSE INCORPORATION INTO ADIPOSE AND MUSCLE TISSUE ......................................................................... 32 Adipose tissue................................................................................................................................................ 32 Muscle tissue................................................................................................................................................. 32 LIPOPROTEIN LIPASE ASSAY............................................................................................................................... 33 Tissue LPL activity........................................................................................................................................ 33 Post-heparin plasma LPL ............................................................................................................................. 34 RESULTS AND COMMENTS.......................................................................................................................... 35 PAPER I .............................................................................................................................................................. 35 PAPER II............................................................................................................................................................. 36 GH, IGF-I and Insulin in the regulation of lipid and lipoprotein metabolism 5 PAPER III ........................................................................................................................................................... 37 PAPER IV ........................................................................................................................................................... 38 DISCUSSION ...................................................................................................................................................... 40 HORMONAL REGULATION OF LPL ACTIVITY...................................................................................................... 40 GH AND IGF-I IN THE REGULATION OF LIPOLYSIS AND LIPOGENESIS ................................................................ 42 GH AND INSULIN IN THE REGULATION OF VLDL SECRETION ............................................................................ 43 THE REGULATION OF APOB AND APOB MRNA EDITING..................................................................................... 46 CONCLUSIONS ................................................................................................................................................. 48 ACKNOWLEDGEMENTS................................................................................................................................ 49 REFERENCES.................................................................................................................................................... 51
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