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1 1. Subgroup Analysis Stratified by Baseline Pancreatic β-cell Function in a Japanese Study of Dulaglutide in Patients with Type 2 Diabetes. Diabetes Ther Feb;9(1): GLP 2. Incidence of diabetes mellitus and neoplasia in Japanese short-statured children treated with growth hormone in the Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS). Clin Pediatr Endocrinol. 2017;26(4): Insulin lispro 25/75 and insulin lispro 50/50 as starter insulin in Japanese patients with type 2 diabetes: subanalysis of the CLASSIFY randomized trial. Endocr J Jul 28;64(7): Analysis of efficacy and safety of dulaglutide 0.75 mg stratified by sex in patients with type 2 diabetes in 2 randomized, controlled phase 3 studies in Japan. Endocr J May 30;64(5): GLP 5. Pancreatic safety in Japanese patients with type 2 diabetes treated with once weekly dulaglutide 0.75 mg up to 52 weeks in phase 3 clinical trials. Endocr J Feb 27;64(2): GLP 6. Caveolin-1 facilitates internalization and degradation of ABCA1 and probucol oxidative products interfere with this reaction to increase HDL biogenesis. Atherosclerosis Oct;253:54-60.

2 HDL ABCA1 HDL 7. Impact of diet on the efficacy of insulin lispro mix 25 and insulin lispro mix 50 as starter insulin in East Asian patients with type 2 diabetes: Subgroup analysis of the Comparison Between Low Mixed Insulin and Mid Mixed Insulin as Starter Insulin For Patients with Type 2 Diabetes Mellitus (CLASSIFY Study) randomized trial. J Diabetes Investig Jan;8(1): Comparison of insulin lispro mix 25 with insulin lispro mix 50 as an insulin starter in Asian patients with type 2 diabetes: a phase 4, open-label, randomized trial (CLASSIFY study). Diabetes Metab Res Rev Jan;33(1). 9. Once-weekly glucagon-like peptide-1 receptor agonist dulaglutide significantly decreases glycated haemoglobin compared with once-daily liraglutide in Japanese patients with type 2 diabetes: 52 weeks of treatment in a randomized phase III study. Diabetes Obes Metab Mar;18(3): Once-weekly glucagon-like peptide-1 receptor agonist dulaglutide is non-inferior to once-daily liraglutide and superior to placebo in Japanese patients with type 2 diabetes: a 26-week randomized phase III study. Diabetes Obes Metab Oct;17(10): GLP HbA1c Subgroup analysis of phase 3 studies of dulaglutide in Japanese patients with type 2 diabetes. Endocr J. 2016;63(3): GLP 12. [Pharmacological profile and clinical trial results of a long-acting, once weekly human GLP-1 receptor agonist Dulaglutide (Genetical Recombination)]. Nihon Yakurigaku Zasshi Oct;146(4): GLP

3 13. Deficiency in the Lipid Exporter ABCA1 Impairs Retrograde Sterol Movement and Disrupts Sterol Sensing at the Endoplasmic Reticulum. J Biol Chem Sep 25;290(39): HDL ABCA1 ABCA1 14. Possible predictors for QOL improvement following GH replacement therapy in adult GHD. Endocr J. 2015;62(8): QOL QOL QOL 15. Effect of growth hormone treatment on quality of life in Japanese children with growth hormone deficiency: an analysis from a prospective observational study. Clin Pediatr Endocrinol Jul;23(3): (QOL) 16. Proteomic analysis of proteins eliminated by low-density lipoprotein apheresis. Ther Apher Dial Feb;18(1): LDL 17. Defining patients at extremely high risk for coronary artery disease in heterozygous familial hypercholesterolemia. J Atheroscler Thromb. 2012;19(4): LDL C

4 18. Calpain-mediated ABCA1 degradation: post-translational regulation of ABCA1 for HDL biogenesis. Biochim Biophys Acta Mar;1821(3): ABCA1 19. HMG-CoA reductase inhibitors enhance phagocytosis by upregulating ATPbinding cassette transporter A7. Atherosclerosis Aug;217(2): ABCA7 ABCA7 ABCA7 20. Protein kinase D regulates the adiponectin gene expression through phosphorylation of AP-2: a common pathway to the ABCA1 gene regulation. Atherosclerosis May;216(1):90-6. ABCA1 AP Roles of ATP-binding cassette transporter A7 in cholesterol homeostasis and host defense system. J Atheroscler Thromb. 2011;18(4): ABCA7 22. Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7. J Lipid Res Sep;51(9): HDL C ABCA7 23. Calmodulin interacts with ATP binding cassette transporter A1 to protect from calpain-mediated degradation and upregulates high-density lipoprotein generation. Arterioscler Thromb Vasc Biol Jul;30(7): ABCA1 HDL 24. Pharmacological inhibition of ABCA1 degradation increases HDL biogenesis and exhibits antiatherogenesis. J Lipid Res Nov;50(11):

5 HDL FGF-1 induces expression of LXRalpha and production of 25-hydroxycholesterol to upregulate the apoe gene in rat astrocytes. J Lipid Res Jun;50(6): FGF HDL E 26. Involvement of protein kinase D in phosphorylation and increase of DNA binding of activator protein 2 alpha to downregulate ATP-binding cassette transporter A1. Arterioscler Thromb Vasc Biol Dec;28(12): AP2 PKD DNA ABCA ApoA-I facilitates ABCA1 recycle/accumulation to cell surface by inhibiting its intracellular degradation and increases HDL generation. Arterioscler Thromb Vasc Biol Oct;28(10): HDL C A-I ABCA1 ABCA1 28. Biogenesis of HDL by SAA is dependent on ABCA1 in the liver in vivo. J Lipid Res Feb;49(2): SAA ABCA1 HDL 29. Telmisartan enhances cholesterol efflux from THP-1 macrophages by activating PPARgamma. J Atheroscler Thromb Jun;14(3): ARB PPARγ ABCA1 30. ATP-binding cassette transporter A1 gene transcription is downregulated by activator protein 2alpha. Doxazosin inhibits activator protein 2alpha and increases high-density lipoprotein biogenesis independent of alpha1-adrenoceptor blockade. Circ Res Jul 20;101(2): α

6 31. ABCA7 expression is regulated by cellular cholesterol through the SREBP2 pathway and associated with phagocytosis. J Lipid Res Sep;47(9): ABCA7 ABCA7 ABCA7 32. Serum amyloid A generates high density lipoprotein with cellular lipid in an ABCA1- or ABCA7-dependent manner. J Lipid Res Jul;47(7): SAA ABCA1 ABCA7 HDL 33. Glucocorticoid receptor regulates ATP-binding cassette transporter-a1 expression and apolipoprotein-mediated cholesterol efflux from macrophages. Arterioscler Thromb Vasc Biol Jan;26(1): Effect of lipid-lowering therapy with atorvastatin on atherosclerotic aortic plaques detected by noninvasive magnetic resonance imaging. J Am Coll Cardiol Mar 1;45(5): MRI 35. Characterization of the expression of TLR2 (toll-like receptor 2) and TLR4 on circulating monocytes in coronary artery disease. J Atheroscler Thromb. 2005;12(1): TLR2 TLR 36. Gln27Glu beta2-adrenergic receptor variant is associated with hypertriglyceridemia and the development of fatty liver. Clin Chim Acta Dec;314(1-2): β

7 β 1. 1 Progress in Medicine( )38 3 Page ( ) 2. 1 GLP-1 1 Progress in Medicine( )36 11 Page ( ) 3. GLP-1 ( ) ( 0.75mg ) ( )51 12 Page ( ) 4. 1 GLP-1 ( ) ( )146 4 Page ( ) 5. ( ) growth hormone Humatrope ( )45 10 Page ( ) 6. 1 Progress in Medicine( )32 8 Page ( ) 7. Update- ( )27 12 Page ( ) 8. FH 4 Progress in Medicine( )31 12 Page ( ) 9. PKD/AP-2 ABCA1 adiponectin ( )53 Page ( ) 10. (ASO) ASO LDL ( )93 4 Page ( ) 11. ASO! ( )93 4 Page ( ) 12.

8 ( )62 5 Page ( ) 13. LDL ( )4520 Page75-74( ) 14. ( 16 ) Life Style Medicine( )4 4 Page ( ) 15. PCSK9 ARH Medical Technology( )38 10 Page ( ) 16. HDL ABCA1 Vascular Medicine( )5 2 Page ( ) 17. Update 2007 ABCA Therapeutic Research( )29 2 Page175( ) 18. ( )52 1 Page13-21( ) 19. E (Effects of Soy Protein on Levels of Remnant-like Particles Cholesterol and Vitamin E in Healthy Men)( ) Journal of Nutritional Science and Vitaminology( )47 4 Page ( ) 20. C-I ( )59 2 ( ) Page ( ) 21. LDL Progress in Medicine( )19 5 Page ( ) 22. ( )25 6 Page ( ) 1. 2 III β ABC ABCA1 2015

9 mg? mg III mg mg ( ) dulaglutide Dulaglutide GLP GHD GH QOL FH LDL-A LDL-Apheresis LDL FH LDL FH PCSK

10 HMG-CoA ABCA LDLR PCSK9 LDL-C LDLR PCSK9 LDL-C CD DPP

11 31. HDL apoa-i ABCA Protein Kinase D AP2 ABCA1 ( ) SAA ABCA FGF-1 apoe-hdl LXR ( ) SAA ABCA1 ( ) HDL ABCA1 HDL SAA-HDL ABCA ATP A7 SREBP SAA HDL LDL ABCA1KO ABCA Serum amyloid A ABCA1 KO ABCA Serum amyloid A HDL ABCA1KO ABCA7

12 (SERM) Malondialdehyde-modified LDL(MDA-LDL) ABCA T CRP THP-1 macrophage ABCA PCPS β2 (codon27), VEGF

13 59. LDL

Low density lipoprotein（LDL）アフェレシス

Low density lipoprotein（LDL）アフェレシス Low density lipoprotein LDL 1 2 1 2 Hisashi MAKINO, Mariko HARADA-SHIBA 1. はじめに Low density lipoprotein LDL 著者連絡先 565-8565 5-7-1 E-mail. mshiba@ncvc.go.jp familial hypercholesterolemia; FH LDL FH LDL 600