Mechanisms of hypoglycemic action of angiotensin peptides in diet induced diabetic mice

MECHANISMS OF HYPOGLYCEMIC ACTION OF ANGIOTENSIN PEPTIDES IN DIET-INDUCED DIABETIC MICE WONG YONG CHIAT B.Sc (Hons.), NUS A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF PHARMACOLOGY NATIONAL UNIVERSITY OF SINGAPORE 2010 ACKNOWLEDGEMENTS I wish to express my sincere gratitude to Associate Professor Sim Meng Kwoon Since knowing him in 2005, he has been an inspiring supervisor, a fantastic mentor and most importantly, a good friend He diligently guided me to successfully complete my PhD degree and showed me the way in becoming a successful researcher I also want to thank him for his patience and words of encouragement that have kept me confident in times of doubts I am deeply impressed with his dedication to Science and research work As a mentor, he shared many of his experiences and positive attitudes to life As a friend, he has put the needs of others before his own and was unstintingly generous with his time I would also like to thank Dr Xu Xiaoguang, my wonderful laboratory officer, for her invaluable assistance and outstanding moral support Working with her has been an enjoyable experience I also wish to express sincere appreciation to National University of Singapore for supporting my PhD full-time research with scholarship Lastly, I am greatly indebted to my loving parents and fiancée Xin Li, who always stand by me with their constant support and unconditional love To them I will always be grateful !"#$%&'(&)'*+%*+,& & & & & & & & -./0& List of publications& List of conference abstracts/ poster presentation& List of figures& List of tables& 31,+&'(&"##4%21"+1'*,& 1! 1! 11! 12! 2! 5677.89& :! );.-!08&:!8?@6)!=?>& A! !"!! #$%%&'()(%&'*+),')-,./&(&+) 0! !"1! 2.(345&'&+,+) 6! !"7! 8'+$9,')+,5'.99,'5)+:+(&;) !1! !"0! &=(4%+) !?! !"@! 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III LIST OF PUBLICATIONS Meng-Kwoon Sim, Xiao-Guang Xu, Yong-Chiat Wong, Sai-Zhen Sim and Kok-Onn Lee, 2007, Des-Aspartate-Angiotensin I Exerts Hypoglycemic Action via Glucose Transporter-4 Translocation in Type Diabetic KKAy Mice and GK Rats Endocrinology, Vol 148, No 12, 5925-5932 Meng-Kwoon Sim, Yong-Chiat Wong, Xiao-Guang Xu, Sai-Zhen Sim and Daniel Tsi, 2009, Hypoglycemic action of chicken meat extract in type diabetic KKAy mice and GK rats, Bioscience, Biotechnology and Biochemistry, Vol 73, 2583-2588 Yong-Chiat Wong and Meng-Kwoon Sim, 2009, Mechanisms of Hypoglycemic Action of Des-Asparate-Angiotensin I in Diet-induced Diabetic Mice, Journal of Diabetes, Vol 1, Issue S1, A230 Yong-Chiat Wong, Meng-Kwoon Sim and Kok-Onn Lee, 2010, Des-aspartateangiotensin I and angiotensin IV attenuate insulin resistance in diet-induced hyperglycaemic mice, [Submitted for Peer Review] LIST OF CONFERENCE ABSTRACTS/ POSTER PRESENTATION Oral presentation, The Inaugural Singapore-Taiwan-Hong Pharmacologists (SINGAPORE, 2007) Kong Meeting of Poster presentation, 3rd International Congress on Prediabetes and the Metabolic Syndrome (Nice, FRANCE, 2009) i LIST OF FIGURES & F=/680& & & & & & !=!30&& & & & & -./0& 1.1 The postulated disease progression of diabetes in developed nations 1.2 The insulin signalling system to metabolic events in the skeletal muscle 14 1.3 The differential of effects on structure and function of IRS-1 17 1.4 The effects of insulin resistance mediating factors in the skeletal muscle 18 1.5 The renin-angiotensin system and its regulating peptidases 21 1.6 The hypothetical IRAP/GLUT4 recycling model 29 1.7 Outline of the experimental strategy 42 2.1 Outline of the experimental protocol of the membrane isolation 54 3.1.1 Effect of DAA-1 on the weight of C57BL/6J mice fed on HFD 62 3.1.2 Effect of Ang-IV on the weight of C57BL/6J mice fed on HFD 63 3.1.3 Effect of DAA-1 on the energy of food consumed by C57BL/6J mice fed on HFD 65 3.1.4 Effect of Ang-IV on the energy of food consumed by C57BL/6J mice fed on HFD 66 3.1.5 Effect of DAA-1 on fasting blood glucose profile in C57BL/6J mice fed on HFD 69 3.1.6 Effect of Ang-IV on fasting blood glucose profile in C57BL/6J mice fed on HFD 70 3.1.7 Effect of DAA-1 on 30-mim OGTT profile in C57BL/6J mice fed on HFD 73 3.1.8 Effect of Ang-IV on 30-mim OGTT profile in C57BL/6J mice fed on HFD 74 3.1.9 Effects of DAA-1 and Ang-IV on the OGTT of C57BL/6J mice fed on HFD 77 3.1.10 Effect of DAA-1 on fasting blood insulin profile in C57BL/6J mice fed on HFD 79 3.1.11 Effect of Ang-IV on fasting blood insulin profile in C57BL/6J mice fed on HFD 80 3.1.12 Effects of DAA-1 and Ang-IV on the serum insulin profile of C57BL/6J mice fed on HFD 82 Effects of DAA-1 and Ang-IV on fasting serum free fatty acid of C57BL/6J mice fed on HFD 84 Experimental outline for the study of the effects of chronic treatment of DAA-1 and Ang-IV on insulin signal transduction in the skeletal muscles of HFD animals 89 3.1.13 3.2.1 ii 3.2.2 Effects of DAA-1 and Ang-IV on basal and insulin-stimulated serine phosphorylation of IR in skeletal muscle of C57BL/ 6J mice fed on HFD 91 3.2.3 Effects of DAA-1 and Ang-IV on basal and insulin-stimulated tyrosine phosphorylation of IR in skeletal muscle of C57BL/6J mice fed on HFD 93 3.2.4 Effects of DAA-1 and Ang-IV on basal and insulin-stimulated serine phosphorylation of IRS-1 in skeletal muscle of C57BL/6J mice fed on HFD 95 3.2.5 Effects of DAA-1 and Ang-IV on basal and insulin-stimulated tyrosine phosphorylation of IRS-1 in skeletal muscle of C57BL/6J mice fed on HFD 97 3.2.6 Effects of DAA-1 and Ang-IV on basal and insulin-stimulated attachment of PI3K to IRS-1 in skeletal muscle of C57BL/6J mice fed on HFD 99 Effects of DAA-1 and Ang-IV on basal and insulin-stimulated phosphorylation of Akt in skeletal muscle of C57BL/6J mice fed on HFD 101 Distribution of GLUT4 protein and enzymatic activity of alkaline phosphodiesterase-1 in membranes of different sucrose gradient fractions 104 Effects of DAA-1 and Ang-IV on insulin-induced GLUT4 translocation in skeletal Muscle of C57BL/6J mice fed on HFD 105 Experimental outline for the study of the effects of chronic treatment of DAA-1 and Ang-IV on oxidative stress and Ang-II signaling induced JNK activation in the skeletal muscle of HFD animals 107 3.2.7 3.2.8 3.2.9 3.3.1 3.3.2 Effects of DAA-1 and Ang-IV on superoxide formation in skeletal muscle of C57BL/6J mice fed on HFD 109 3.3.3 Effects of DAA-1 and Ang-IV on the expression of gp91 NADPH oxidase in skeletal muscle of C57BL/6J mice fed on HFD 110 Effects of DAA-1 and Ang-IV on basal and insulin-stimulated level of phosphorylated JNK in skeletal muscle of C57BL/6J mice fed on HFD 112 Effects of DAA-1 and Ang-IV on the coupling of JAK-2, IRS-1 and PI3K to the angiotensin AT1 receptor in skeletal muscle of C57BL/6J mice fed on HFD 114 Effects of DAA-1 and Ang-IV on basal and insulin-stimulated IRAP-PI3K interaction in skeletal muscle of C57BL/6J mice fed on HFD 116 Effects of AT1 and AT4 receptor blockers on hypoglycaemic actions of DAA-I and Ang-IV in C57BL/6J mice 118 3.6.2 Effect of losartan on the hypoglycemic action of DAA-I in C57BL/6J mice 119 3.7.1 Effects of Ang-IV and its metabolites on blood glucose of C57BL/6J mice 121 3.8.1 Effect of hyperglycaemia condition on the survival of pancreatic beta-TC-6 cells 123 3.8.2 Effect of DAA-1 on the survival of pancreatic beta-TC-6 cells cultured in high glucose concentration 124 3.3.4 3.4.1 3.5.1 3.6.1 iii 3.8.3 3.8.4 Effect of Ang-IV on the survival of pancreatic beta-TC-6 cells cultured in high glucose concentration 125 Effect of losartan on the survival of pancreatic beta-TC-6 cells cultured in high glucose concentration 126 3.8.5 Effect of DAA-1 in the presence of losartan on the survival of pancreatic beta-TC-6 cells cultured in high glucose concentration 127 3.8.6 Effects of DAA-1, Ang-IV and losartan on the survival of pancreatic beta-TC-6 cells cultured in basal medium 128 4.1 Early events of the Ang-II and insulin signalling cross-talk 137 4.2 Putative mechanism of hypoglycaemic action of DAA-1 136 4.3 Putative mechanism of hypoglycaemic action of Ang-IV 141 LIST OF TABLES & !.I30& & & & & !=!30&& & & & & -./0& 1.1 Summary of evidences of Ang-II as mediator in obesity related diseases 33 1.2 Current medications available for glycemic control 39 2.1 Diet composition of normal diet and high-fat high-sucrose diet 44 2.2 List of antibodies 57 3.1.1 Animal characteristics 87 4.1 Summary of various protein expressions in tissues of the test animals 131 & iv 31,+&'(&.##4%21"+1'*,& ACE ACD Akt Ang-I Ang-II Ang-III Ang-IV ANOVA ARB AT1 AT2 AT4 BSA DAA-1 DAG DHE DMEM ELISA FFA GLUT4 GLP GK GPCR h HFD IB IR IRAP IRS-1 IP i.p JAK2 JNK kg MAPK mg MTT !g mM !M NADPH ND Angiotensin converting enzyme Acyl-coenzyme A dehydrogenase Protein kinase B Angiotensin I Angiotensin II Angiotensin III Angiotensin IV One-way analysis of variance Angiotensin receptor blocker Angiotensin II receptor type one Angiotensin II receptor type two Angiotensin IV receptor Bovine serum albumin Des-aspartate-angiotensin I Diacyglycerol Dihydroethidium Dulbecco’s modified Eagle’s medium Enzyme linked immunosorbent assay Free fatty acid Glucose transporter Glucagon-like protein Goto-Kakizaki rats G-protein coupled receptor Hour High-fat high-sucrose diet Immunoblot Insulin receptor Insulin-regulated aminopeptidase Insulin receptor substrate Immunoprecipitation Intraperitoneal injection Janus kinase Jun N-terminal kinase Kilogram Mitogen-activated protein kinase Milligram 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Microgram Minute Millimolar Micromolar Nicotinamide adenine dinucleotide phosphate Normal diet v Eguchi S, Numaguchi K, Iwasaki H, Matsumoto T, Yamakawa T, Utsunomiya H, Motley E, Kawakatsu H, Owada K, Hirata Y, et al 1998 Calcium-dependent epidermal growth factor receptor transactivation mediates the angiotensin II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells J Biol Chem 273 8890-8896 Engelmann M, Wotjak C, Neumann I, Ludwig M & Landgraf R 1996 Behavioral consequences of intracerebral vasopressin and oxytocin: focus on learning and memory Neurosci Biobehav Rev 20 341-358 Esposito DL, Li Y, Cama A & Quon MJ 2001 Tyr(612) and Tyr(632) in human insulin receptor substrate-1 are important for full activation of insulin-stimulated phosphatidylinositol 3-kinase activity and translocation of GLUT4 in adipose cells Endocrinology 142 2833-2840 Esposito K, Ciotola M, Schisano B, Misso L, Giannetti G, Ceriello A & Giugliano D 2006 Oxidative stress in the metabolic syndrome J Endocrinol Invest 29 791-795 Esteban V, Ruperez M, Sánchez-López E, Rodríguez-Vita J, Lorenzo O, Demaegdt H, Vanderheyden P, Egido J & Ruiz-Ortega M 2005 Angiotensin IV activates the nuclear transcription factor-kappaB and related proinflammatory genes in vascular smooth muscle cells Circ Res 96 965-973 Farah V, Elased KM & Morris M 2007 Genetic and dietary interactions: role of angiotensin AT1a receptors in response to a high-fructose diet Am J Physiol Heart Circ Physiol 293 H1083-1089 Faure S, Javellaud J, Achard J & Oudart N 2006 Vasoconstrictive effect of angiotensin IV in isolated rat basilar artery independent of AT1 and AT2 receptors J Vasc Res 43 1926 Ferrario C, Chappell M, Tallant E, Brosnihan K & Diz D 1997 Counterregulatory actions of angiotensin-(1-7) Hypertension 30 535-541 Ferrario C, Trask A & Jessup J 2005 Advances in biochemical and functional roles of angiotensin-converting enzyme and angiotensin-(1-7) in regulation of cardiovascular function Am J Physiol Heart Circ Physiol 289 H2281-2290 Fex M, Nitert M, Wierup N, Sundler F, Ling C & Mulder H 2007 Enhanced mitochondrial metabolism may account for the adaptation to insulin resistance in islets from C57BL/6J mice fed a high-fat diet Diabetologia 50 74-83 Fitzgerald S, Evans R, Bergström G & Anderson W 1999 Renal hemodynamic responses to intrarenal infusion of ligands for the putative angiotensin IV receptor in anesthetized rats J Cardiovasc Pharmacol 34 206-211 154 Fliser D, Schaefer F, Schmid D, Veldhuis J & Ritz E 1997 Angiotensin II affects basal, pulsatile, and glucose-stimulated insulin secretion in humans Hypertension 30 11561161 Folli F, Kahn CR, Hansen H, Bouchie JL & Feener EP 1997 Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels A potential role for serine phosphorylation in insulin/angiotensin II crosstalk J Clin Invest 100 2158-2169 Fraser G 1999 Associations between diet and cancer, ischemic heart disease, and allcause mortality in non-Hispanic white California Seventh-day Adventists Am J Clin Nutr 70 532S-538S Fuhlendorff J, Rorsman P, Kofod H, Brand C, Rolin B, MacKay P, Shymko R & Carr R 1998 Stimulation of insulin release by repaglinide and glibenclamide involves both common and distinct processes Diabetes 47 345-351 Gaetaniello L, Fiore M, de Filippo S, Pozzi N, Tamasi S & Pignata C 1998 Occupancy of dipeptidyl peptidase IV activates an associated tyrosine kinase and triggers an apoptotic signal in human hepatocarcinoma cells Hepatology 27 934-942 Gan S, Barr J, Arieff A & Pearl R 1992 Biguanide-associated lactic acidosis Case report and review of the literature Arch Intern Med 152 2333-2336 Gao Z, Zhang X, Zuberi A, Hwang D, Quon M, Lefevre M & Ye J 2004 Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3T3L1 adipocytes Mol Endocrinol 18 2024-2034 Garvey W, Olefsky J, Matthaei S & Marshall S 1987 Glucose and insulin co-regulate the glucose transport system in primary cultured adipocytes A new mechanism of insulin resistance J Biol Chem 262 189-197 Genest J, Cantin M, Garcia R, Thibault G, Gutkowska J, Schiffrin E, Kuchel O & Hamet P 1983 Extrarenal angiotensin-forming enzymes Clin Exp Hypertens A 1065-1080 Giani J, Gironacci M, Muñoz M, Peña C, Turyn D & Dominici F 2007 Angiotensin-(1 7) stimulates the phosphorylation of JAK2, IRS-1 and Akt in rat heart in vivo: role of the AT1 and Mas receptors Am J Physiol Heart Circ Physiol 293 H1154-1163 Giovannucci E, Rimm E, Colditz G, Stampfer M, Ascherio A, Chute C & Willett W 1993 A prospective study of dietary fat and risk of prostate cancer J Natl Cancer Inst 85 15711579 Giugliano D, Ceriello A & Esposito K 2006 The effects of diet on inflammation: emphasis on the metabolic syndrome J Am Coll Cardiol 48 677-685 155 Golovchenko I, Goalstone M, Watson P, Brownlee M & Draznin B 2000 Hyperinsulinemia enhances transcriptional activity of nuclear factor-kappaB induced by angiotensin II, hyperglycemia, and advanced glycosylation end products in vascular smooth muscle cells Circ Res 87 746-752 Gronholm T, Cheng ZJ, Palojoki E, Eriksson A, Backlund T, Vuolteenaho O, Finckenberg P, Laine M, Mervaala E & Tikkanen I 2005 Vasopeptidase inhibition has beneficial cardiac effects in spontaneously diabetic Goto-Kakizaki rats Eur J Pharmacol 519 267-276 Grunberger G, Jen K & Artiss J 2007 The benefits of early intervention in obese diabetic patients with FBCx: a new dietary fibre Diabetes Metab Res Rev 23 56-62 Halton T, Willett W, Liu S, Manson J, Stampfer M & Hu F 2006 Potato and french fry consumption and risk of type diabetes in women Am J Clin Nutr 83 284-290 Hamilton T, Handa R, Harding J & Wright J 2001 A role for the angiotensin IV/AT4 system in mediating natriuresis in the rat Peptides 22 935-944 Handa R 2001 Characterization and signaling of the AT(4) receptor in human proximal tubule epithelial (HK-2) cells J Am Soc Nephrol 12 440-449 Handa R 2006 Biphasic actions of angiotensin IV on renal blood flow in the rat Regul Pept 136 23-29 Handa R, Harding J & Simasko S 1999 Characterization and function of the bovine kidney epithelial angiotensin receptor subtype using angiotensin IV and divalinal angiotensin IV as receptor ligands J Pharmacol Exp Ther 291 1242-1249 Heaton K, Marcus S, Emmett P & Bolton C 1988 Particle size of wheat, maize, and oat test meals: effects on plasma glucose and insulin responses and on the rate of starch digestion in vitro Am J Clin Nutr 47 675-682 Hegen M, Mittrücker H, Hug R, Demuth H, Neubert K, Barth A & Fleischer B 1993 Enzymatic activity of CD26 (dipeptidylpeptidase IV) is not required for its signalling function in T cells Immunobiology 189 483-493 Helmersson J, Vessby B, Larsson A & Basu S 2004 Association of type diabetes with cyclooxygenase-mediated inflammation and oxidative stress in an elderly population Circulation 109 1729-1734 Henry R, Scheaffer L & Olefsky J 1985 Glycemic effects of intensive caloric restriction and isocaloric refeeding in noninsulin-dependent diabetes mellitus J Clin Endocrinol Metab 61 917-925 156 Hermann L, Scherstén B, Bitzén P, Kjellström T, Lindgärde F & Melander A 1994 Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations A double-blind controlled study Diabetes Care 17 1100-1109 Higueruelo S, Vaquero M, Pastor C, Galimany R & Romero R 1998 Fosinopril ameliorates exogenous cholesterol-induced incipient glomerular lesions in obese Zucker rats Effects on eicosanoid secretion Nephrol Dial Transplant 13 2227-2233 Hilchey S & Bell-Quilley C 1995 Association between the natriuretic action of angiotensin-(1-7) and selective stimulation of renal prostaglandin I2 release Hypertension 25 1238-1244 Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M & Hotamisligil GS 2002 A central role for JNK in obesity and insulin resistance Nature 420 333-336 Hojima Y, Yamashita M, Ochi N, Moriwaki C & Moriya H 1977 Isolation and some properties of dog and rat pancreatic kallikreins J Biochem 81 599-610 Hollander P, Levy P, Fineman M, Maggs D, Shen L, Strobel S, Weyer C & Kolterman O 2003 Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type diabetes: a 1-year randomized controlled trial Diabetes Care 26 784-790 Holman R, Cull C & Turner R 1999 A randomized double-blind trial of acarbose in type diabetes shows improved glycemic control over years (U.K Prospective Diabetes Study 44) Diabetes Care 22 960-964 Holstein A, Plaschke A & Egberts E Lower incidence of severe hypoglycaemia in patients with type diabetes treated with glimepiride versus glibenclamide Diabetes Metab Res Rev 17 467-473 Horio H & Ohtsuru M 2001 Maitake (Grifola frondosa) improve glucose tolerance of experimental diabetic rats J Nutr Sci Vitaminol (Tokyo) 47 57-63 Hotamisligil GS, Shargill NS & Spiegelman BM 1993 Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance Science 259 87-91 Inzucchi S, Maggs D, Spollett G, Page S, Rife F, Walton V & Shulman G 1998 Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus N Engl J Med 338 867-872 Ishida M, Marrero M, Schieffer B, Ishida T, Bernstein K & Berk B 1995 Angiotensin II activates pp60c-src in vascular smooth muscle cells Circ Res 77 1053-1059 157 Jauch K, Hartl W, Guenther B, Wicklmayr M, Rett K & Dietze G 1987 Captopril enhances insulin responsiveness of forearm muscle tissue in non-insulin-dependent diabetes mellitus Eur J Clin Invest 17 448-454 Jenkins D, Wolever T & Jenkins A 1988 Starchy foods and glycemic index Diabetes Care 11 149-159 Johnson A, Lampson M & McGraw T 2001 A di-leucine sequence and a cluster of acidic amino acids are required for dynamic retention in the endosomal recycling compartment of fibroblasts Mol Biol Cell 12 367-381 Johnston C 1990 Biochemistry and pharmacology of the renin-angiotensin system Drugs 39 Suppl 21-31 Jönsson A, Rydberg T, Ekberg G, Hallengren B & Melander A 1994 Slow elimination of glyburide in NIDDM subjects Diabetes Care 17 142-145 Kahn CR 1994 Banting Lecture Insulin action, diabetogenes, and the cause of type II diabetes Diabetes 43 1066-1084 Kasuga M, Fujita-Yamaguchi Y, Blithe D & Kahn C 1983 Tyrosine-specific protein kinase activity is associated with the purified insulin receptor Proc Natl Acad Sci U S A 80 2137-2141 Keller S, Scott H, Mastick C, Aebersold R & Lienhard G 1995 Cloning and characterization of a novel insulin-regulated membrane aminopeptidase from Glut4 vesicles J Biol Chem 270 23612-23618 Kelly K & Laychock S 1981 Prostaglandin synthesis and metabolism in isolated pancreatic islets of the rat Prostaglandins 21 759-769 Kerins D, Hao Q & Vaughan D 1995 Angiotensin induction of PAI-1 expression in endothelial cells is mediated by the hexapeptide angiotensin IV J Clin Invest 96 25152520 King H & Rewers M 1993 Global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults WHO Ad Hoc Diabetes Reporting Group Diabetes Care 16 157-177 Kong M, Stubbs T, King P, Macdonald I, Lambourne J, Blackshaw P, Perkins A & Tattersall R 1998 The effect of single doses of pramlintide on gastric emptying of two meals in men with IDDM Diabetologia 41 577-583 Korec R 2002 Heine RJ, Dekker JM (2002) Beyond postprandial hyperglycaemia: metabolic factors associated with cardiovascular disease Diabetologia 45:461-475 Diabetologia 45 1349 158 Kouyama R, Suganami T, Nishida J, Tanaka M, Toyoda T, Kiso M, Chiwata T, Miyamoto Y, Yoshimasa Y, Fukamizu A, et al 2005 Attenuation of diet-induced weight gain and adiposity through increased energy expenditure in mice lacking angiotensin II type 1a receptor Endocrinology 146 3481-3489 Kramer HJ, Nguyen QD, Curhan G & Hsu CY 2003 Renal insufficiency in the absence of albuminuria and retinopathy among adults with type diabetes mellitus JAMA 289 3273-3277 Kurtz T & Pravenec M 2004 Antidiabetic mechanisms of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists: beyond the renin-angiotensin system J Hypertens 22 2253-2261 Kähne T, Reinhold D, Neubert K, Born I, Faust J & Ansorge S 2000 Signal transduction events induced or affected by inhibition of the catalytic activity of dipeptidyl peptidase IV (DP IV, CD26) Adv Exp Med Biol 477 131-137 Le M, Vanderheyden P, Szaszák M, Hunyady L & Vauquelin G 2002 Angiotensin IV is a potent agonist for constitutive active human AT1 receptors Distinct roles of the N-and Cterminal residues of angiotensin II during AT1 receptor activation J Biol Chem 277 23107-23110 Lebovitz H, Dole J, Patwardhan R, Rappaport E & Freed M 2001 Rosiglitazone monotherapy is effective in patients with type diabetes J Clin Endocrinol Metab 86 280-288 Lee J, Chai S, Mendelsohn F, Morris M & Allen A 2001 Potentiation of cholinergic transmission in the rat hippocampus by angiotensin IV and LVV-hemorphin-7 Neuropharmacology 40 618-623 Lee J, Mustafa T, McDowall S, Mendelsohn F, Brennan M, Lew R, Albiston A & Chai S 2003 Structure-activity study of LVV-hemorphin-7: angiotensin AT4 receptor ligand and inhibitor of insulin-regulated aminopeptidase J Pharmacol Exp Ther 305 205-211 Lee JH, Palaia T & Ragolia L 2009 Impaired insulin-mediated vasorelaxation in diabetic Goto-Kakizaki rats is caused by impaired Akt phosphorylation Am J Physiol Cell Physiol 296 C327-338 Leighton B, Budohoski L, Lozeman FJ, Challiss RA & Newsholme EA 1985 The effect of prostaglandins E1, E2 and F2 alpha and indomethacin on the sensitivity of glycolysis and glycogen synthesis to insulin in stripped soleus muscles of the rat Biochem J 227 337-340 159 Leighton B, Challiss RA & Newsholme EA 1990 The role of prostaglandins as modulators of insulin-stimulated glucose metabolism in skeletal muscle Horm Metab Res Suppl 22 89-95 Leung K & Leung P 2008 Effects of hyperglycemia on angiotensin II receptor type expression and insulin secretion in an INS-1E pancreatic beta-cell line JOP 290-299 Leung P, Chan H, Fu L & Wong P 1997 Localization of angiotensin II receptor subtypes AT1 and AT2 in the pancreas of rodents J Endocrinol 153 269-274 Leung P, Chan H & Wong P 1998 Immunohistochemical localization of angiotensin II in the mouse pancreas Histochem J 30 21-25 Leung P, Chan W, Wong T & Sernia C 1999 Expression and localization of the reninangiotensin system in the rat pancreas J Endocrinol 160 13-19 Lew R, Mustafa T, Ye S, McDowall S, Chai S & Albiston A 2003 Angiotensin AT4 ligands are potent, competitive inhibitors of insulin regulated aminopeptidase (IRAP) J Neurochem 86 344-350 Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R & Raz I 2001 Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type diabetes N Engl J Med 345 851-860 Li X, Campbell D, Ohishi M, Yuan S & Zhuo J 2006 AT1 receptor-activated signaling mediates angiotensin IV-induced renal cortical vasoconstriction in rats Am J Physiol Renal Physiol 290 F1024-1033 Li Y, Block E & Patel J 2002 Activation of multiple signaling modules is critical in angiotensin IV-induced lung endothelial cell proliferation Am J Physiol Lung Cell Mol Physiol 283 L707-716 Li Y, Xu W, Liao Z, Yao B, Chen X, Huang Z, Hu G & Weng J 2004 Induction of longterm glycemic control in newly diagnosed type diabetic patients is associated with improvement of beta-cell function Diabetes Care 27 2597-2602 Lillioja S, Nyomba B, Saad M, Ferraro R, Castillo C, Bennett P & Bogardus C 1991 Exaggerated early insulin release and insulin resistance in a diabetes-prone population: a metabolic comparison of Pima Indians and Caucasians J Clin Endocrinol Metab 73 866876 Liu Y, Herschkovitz A, Boura-Halfon S, Ronen D, Paz K, Leroith D & Zick Y 2004 Serine phosphorylation proximal to its phosphotyrosine binding domain inhibits insulin receptor substrate function and promotes insulin resistance Mol Cell Biol 24 96689681 160 Lo H, Tu S, Lin K & Lin S 2004 The anti-hyperglycemic activity of the fruiting body of Cordyceps in diabetic rats induced by nicotinamide and streptozotocin Life Sci 74 28972908 Lu J, Zhang J, Block E & Patel J 2005 Angiotensin IV enhances phosphorylation of 4EBP1 by multiple signaling events in lung endothelial cells Mol Cell Biochem 275 181188 Martin S, Rice J, Gould G, Keller S, Slot J & James D 1997 The glucose transporter GLUT4 and the aminopeptidase vp165 colocalise in tubulo-vesicular elements in adipocytes and cardiomyocytes J Cell Sci 110 ( Pt 18) 2281-2291 Martínez-Martos J & Ramírez-Expósito M 2006 Dietary fat and hypertension: a novel approach through the proteolytic regulatory enzymes of the renin-angiotensin-system Cardiovasc Hematol Agents Med Chem 263-276 Matsuda M & DeFronzo R 1999 Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp Diabetes Care 22 14621470 Meneilly G, Ryan E, Radziuk J, Lau D, Yale J, Morais J, Chiasson J, Rabasa-Lhoret R, Maheux P, Tessier D, et al 2000 Effect of acarbose on insulin sensitivity in elderly patients with diabetes Diabetes Care 23 1162-1167 Miller J & Colagiuri S 1994 The carnivore connection: dietary carbohydrate in the evolution of NIDDM Diabetologia 37 1280-1286 Min L, Sim MK & Xu XG 2000 Effects of des-aspartate-angiotensin I on angiotensin IIinduced incorporation of phenylalanine and thymidine in cultured rat cardiomyocytes and aortic smooth muscle cells Regul Pept 95 93-97 Mittrücker H, Steeg C, Malissen B & Fleischer B 1995 The cytoplasmic tail of the T cell receptor zeta chain is required for signaling via CD26 Eur J Immunol 25 295-297 Miura T, Kubo M, Itoh Y, Iwamoto N, Kato M, Park S, Ukawa Y, Kita Y & Suzuki I 2002 Antidiabetic activity of Lyophyllum decastes in genetically type diabetic mice Biol Pharm Bull 25 1234-1237 Moan A, Risanger T, Eide I & Kjeldsen S 1994 The effect of angiotensin II receptor blockade on insulin sensitivity and sympathetic nervous system activity in primary hypertension Blood Press 185-188 Natali A & Ferrannini E 2004 Hypertension, insulin resistance, and the metabolic syndrome Endocrinol Metab Clin North Am 33 417-429 161 Nesto R, Bell D, Bonow R, Fonseca V, Grundy S, Horton E, Le Winter M, Porte D, Semenkovich C, Smith S, et al 2003 Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association October 7, 2003 Circulation 108 2941-2948 Niskanen L, Uusitupa M, Sarlund H, Siitonen O & Pyörälä K 1990 Five-year follow-up study on plasma insulin levels in newly diagnosed NIDDM patients and nondiabetic subjects Diabetes Care 13 41-48 Norris S, Zhang X, Avenell A, Gregg E, Bowman B, Serdula M, Brown T, Schmid C & Lau J 2004 Long-term effectiveness of lifestyle and behavioral weight loss interventions in adults with type diabetes: a meta-analysis Am J Med 117 762-774 Paolisso G, Di Maro G, D'Amore A, Passariello N, Gambardella A, Varricchio M & D'Onofrio F 1995a Low-dose iloprost infusion improves insulin action in aged healthy subjects and NIDDM patients Diabetes Care 18 200-205 Paolisso G, Tataranni PA, Foley JE, Bogardus C, Howard BV & Ravussin E 1995b A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM Diabetologia 38 1213-1217 Papadimitriou A, King A, Jones P & Persaud S 2007 Anti-apoptotic effects of arachidonic acid and prostaglandin E2 in pancreatic beta-cells Cell Physiol Biochem 20 607-616 Peach M 1977 Renin-angiotensin system: biochemistry and mechanisms of action Physiol Rev 57 313-370 Pelicci G, Lanfrancone L, Grignani F, McGlade J, Cavallo F, Forni G, Nicoletti I, Pawson T & Pelicci P 1992 A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction Cell 70 93-104 Phillips L, Grunberger G, Miller E, Patwardhan R, Rappaport E & Salzman A 2001 Once- and twice-daily dosing with rosiglitazone improves glycemic control in patients with type diabetes Diabetes Care 24 308-315 Phillips M, Speakman E & Kimura B 1993 Levels of angiotensin and molecular biology of the tissue renin angiotensin systems Regul Pept 43 1-20 Phillips M & Sumners C 1998 Angiotensin II in central nervous system physiology Regul Pept 78 1-11 Prada P, Zecchin H, Gasparetti A, Torsoni M, Ueno M, Hirata A, Corezola Amaral M, Höer N, Boschero A & Saad M 2005 Western diet modulates insulin signaling, c-Jun Nterminal kinase activity, and insulin receptor substrate-1ser307 phosphorylation in a tissue-specific fashion Endocrinology 146 1576-1587 162 Ratner R, Want L, Fineman M, Velte M, Ruggles J, Gottlieb A, Weyer C & Kolterman O 2002 Adjunctive therapy with the amylin analogue pramlintide leads to a combined improvement in glycemic and weight control in insulin-treated subjects with type diabetes Diabetes Technol Ther 51-61 Reaven G, Abbasi F & McLaughlin T 2004 Obesity, insulin resistance, and cardiovascular disease Recent Prog Horm Res 59 207-223 Reid I, Morris B & Ganong W 1978 The renin-angiotensin system Annu Rev Physiol 40 377-410 Reiter CE, Wu X, Sandirasegarane L, Nakamura M, Gilbert KA, Singh RS, Fort PE, Antonetti DA & Gardner TW 2006 Diabetes reduces basal retinal insulin receptor signaling: reversal with systemic and local insulin Diabetes 55 1148-1156 Ridgeway CE, Jaffe RB, Braunstein GD, Bray G, Drucker DJ, Goldstein BJ, Jensen MD, Kaufman FR, Seely EW, Thomas MK, et al 2004 The Endocrine Society Weighs In: A handbook on obesity in America (1st ed.) MD: The Endocrine Society Rogi T, Tsujimoto M, Nakazato H, Mizutani S & Tomoda Y 1996 Human placental leucine aminopeptidase/oxytocinase A new member of type II membrane-spanning zinc metallopeptidase family J Biol Chem 271 56-61 Rosen O 1986 Insulin receptor as a tyrosine protein kinase Ann N Y Acad Sci 463 13-19 Ross S, Scott H, Morris N, Leung W, Mao F, Lienhard G & Keller S 1996 Characterization of the insulin-regulated membrane aminopeptidase in 3T3-L1 adipocytes J Biol Chem 271 3328-3332 Rother K 2007 Diabetes treatment bridging the divide N Engl J Med 356 1499-1501 Rydberg T, Jönsson A, Røder M & Melander A 1994 Hypoglycemic activity of glyburide (glibenclamide) metabolites in humans Diabetes Care 17 1026-1030 Saad M, Velloso L & Carvalho C 1995 Angiotensin II induces tyrosine phosphorylation of insulin receptor substrate and its association with phosphatidylinositol 3-kinase in rat heart Biochem J 310 ( Pt 3) 741-744 Sardinia M, Hanesworth J, Krebs L & Harding J AT4 receptor binding characteristics: Damino acid- and glycine-substituted peptides Peptides 14 949-954 Schlingemann RO, Hofman P, Vrensen GF & Blaauwgeers HG 1999 Increased expression of endothelial antigen PAL-E in human diabetic retinopathy correlates with microvascular leakage Diabetologia 42 596-602 163 Schneider SH, Khachadurian AK, Amorosa LF, Clemow L & Ruderman NB 1992 Tenyear experience with an exercise-based outpatient life-style modification program in the treatment of diabetes mellitus Diabetes Care 15 1800-1810 Schraer C, Lanier A, Boyko E, Gohdes D & Murphy N 1988 Prevalence of diabetes mellitus in Alaskan Eskimos, Indians, and Aleuts Diabetes Care 11 693-700 Shibata K, Kajiyama H, Ino K, Nawa A, Nomura S, Mizutani S & Kikkawa F 2007 PLAP/IRAP-induced cell proliferation and glucose uptake in endometrial carcinoma cells via insulin receptor signaling BMC Cancer 15 Shipp M & Look A 1993 Hematopoietic differentiation antigens that are membraneassociated enzymes: cutting is the key! Blood 82 1052-1070 Shiuchi T, Cui TX, Wu L, Nakagami H, Takeda-Matsubara Y, Iwai M & Horiuchi M 2002 ACE inhibitor improves insulin resistance in diabetic mouse via bradykinin and NO Hypertension 40 329-334 Sim M & Radhakrishnan R 1994 Novel central action of des-Asp-angiotensin I Eur J Pharmacol 257 R1-3 Sim MK, Choo MH & Qiu XS 1994 Degradation of angiotensin I to [desAsp1]angiotensin I by a novel aminopeptidase in the rat hypothalamus Biochem Pharmacol 48 1043-1046 Sim MK & Min L 1998 Effects of des-Asp-angiotensin I on experimentally-induced cardiac hypertrophy in rats Int J Cardiol 63 223-227 Sim MK & Qiu XS 1994 Formation of des-Asp-angiotensin I in the hypothalamic extract of normo- and hypertensive rats Blood Press 260-264 Sim MK, Xu XG, Wong YC, Sim SZ & Lee KO 2007 Des-aspartate-angiotensin I exerts hypoglycemic action via GLUT4 translocation in type diabetic KKAy mice and GK rats Endocrinology Song Y, Manson J, Buring J & Liu S 2004 A prospective study of red meat consumption and type diabetes in middle-aged and elderly women: the women's health study Diabetes Care 27 2108-2115 Speedy A 2003 Global production and consumption of animal source foods J Nutr 133 4048S-4053S Stang M, Wysowski D & Butler-Jones D 1999 Incidence of lactic acidosis in metformin users Diabetes Care 22 925-927 164 Stragier B, Demaegdt H, De Bundel D, Smolders I, Sarre S, Vauquelin G, Ebinger G, Michotte Y & Vanderheyden P 2007 Involvement of insulin-regulated aminopeptidase and/or aminopeptidase N in the angiotensin IV-induced effect on dopamine release in the striatum of the rat Brain Res 1131 97-105 Stragier B, Sarre S, Vanderheyden P, Vauquelin G, Fournié-Zaluski M, Ebinger G & Michotte Y 2004 Metabolism of angiotensin II is required for its in vivo effect on dopamine release in the striatum of the rat J Neurochem 90 1251-1257 Stumvoll M, Goldstein B & van Haeften T Type diabetes: principles of pathogenesis and therapy Lancet 365 1333-1346 Sugiura M, Ohshima M, Ogawa K & Yano M 2006 Chronic administration of Satsuma mandarin fruit (Citrus unshiu Marc.) improves oxidative stress in streptozotocin-induced diabetic rat liver Biol Pharm Bull 29 588-591 Sumitani S, Ramlal T, Somwar R, Keller S & Klip A 1997 Insulin regulation and selective segregation with glucose transporter-4 of the membrane aminopeptidase vp165 in rat skeletal muscle cells Endocrinology 138 1029-1034 Surwit R, Feinglos M, Rodin J, Sutherland A, Petro A, Opara E, Kuhn C & RebufféScrive M 1995 Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6J and A/J mice Metabolism 44 645-651 Surwit R, Kuhn C, Cochrane C, McCubbin J & Feinglos M 1988 Diet-induced type II diabetes in C57BL/6J mice Diabetes 37 1163-1167 Tahmasebi M, Puddefoot J, Inwang E & Vinson G 1999 The tissue renin-angiotensin system in human pancreas J Endocrinol 161 317-322 Tessier D, Dawson K, Tétrault J, Bravo G & Meneilly G 1994 Glibenclamide vs gliclazide in type diabetes of the elderly Diabet Med 11 974-980 Thomas W & Mendelsohn F 2003 Angiotensin receptors: form and function and distribution Int J Biochem Cell Biol 35 774-779 Thorburn A, Brand J, O'Dea K, Spargo R & Truswell A 1987 Plasma glucose and insulin responses to starchy foods in Australian aborigines: a population now at high risk of diabetes Am J Clin Nutr 46 282-285 Tikellis C, Wookey PJ, Candido R, Andrikopoulos S, Thomas MC & Cooper ME 2004 Improved islet morphology after blockade of the renin- angiotensin system in the ZDF rat Diabetes 53 989-997 165 Timmermans P, Wong P, Chiu A, Herblin W, Benfield P, Carini D, Lee R, Wexler R, Saye J & Smith R 1993 Angiotensin II receptors and angiotensin II receptor antagonists Pharmacol Rev 45 205-251 Tucker M & Turcotte L 2002 Impaired fatty acid oxidation in muscle of aging rats perfused under basal conditions Am J Physiol Endocrinol Metab 282 E1102-1109 Turner R, Cull C, Frighi V & Holman R 1999 Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49) UK Prospective Diabetes Study (UKPDS) Group JAMA 281 2005-2012 Unger T, Badoer E, Ganten D, Lang R & Rettig R 1988 Brain angiotensin: pathways and pharmacology Circulation 77 I40-54 Uusitupa M, Laitinen J, Siitonen O, Vanninen E & Pyorala K 1993 The maintenance of improved metabolic control after intensified diet therapy in recent type diabetes Diabetes Res Clin Pract 19 227-238 van Dam R, Willett W, Rimm E, Stampfer M & Hu F 2002 Dietary fat and meat intake in relation to risk of type diabetes in men Diabetes Care 25 417-424 van Rodijnen W, van Lambalgen T, van Wijhe M, Tangelder G & Ter Wee P 2002 Renal microvascular actions of angiotensin II fragments Am J Physiol Renal Physiol 283 F8692 Velloso L, Folli F, Sun X, White M, Saad M & Kahn C 1996 Cross-talk between the insulin and angiotensin signaling systems Proc Natl Acad Sci U S A 93 12490-12495 Vercruysse L, Morel N, Van Camp J, Szust J & Smagghe G 2008 Antihypertensive mechanism of the dipeptide Val-Tyr in rat aorta Peptides 29 261-267 Vidal-Puig A, Considine R, Jimenez-Liñan M, Werman A, Pories W, Caro J & Flier J 1997 Peroxisome proliferator-activated receptor gene expression in human tissues Effects of obesity, weight loss, and regulation by insulin and glucocorticoids J Clin Invest 99 2416-2422 Wada T, Inada Y, Sanada T, Ojima M, Shibouta Y, Noda M & Nishikawa K 1994 Effect of an angiotensin II receptor antagonist, CV-11974, and its prodrug, TCV-116, on production of aldosterone Eur J Pharmacol 253 27-34 Wallberg-Henriksson H, Constable S, Young D & Holloszy J 1988 Glucose transport into rat skeletal muscle: interaction between exercise and insulin J Appl Physiol 65 909-913 166 Wallis M, Lankford M & Keller S 2007 Vasopressin is a physiological substrate for the insulin-regulated aminopeptidase IRAP Am J Physiol Endocrinol Metab 293 E10921102 Wang CH, Leung N, Lapointe N, Szeto L, Uffelman KD, Giacca A, Rouleau JL & Lewis GF 2003 Vasopeptidase inhibitor omapatrilat induces profound insulin sensitization and increases myocardial glucose uptake in Zucker fatty rats: Studies comparing a vasopeptidase inhibitor, angiotensin-converting enzyme inhibitor, and angiotensin II type I receptor blocker Circulation 107 1923-1929 Wasner H, Weber S, Partke H & Amini-Hadi-Kiashar H 1994 Indomethacin treatment causes loss of insulin action in rats: involvement of prostaglandins in the mechanism of insulin action Acta Diabetol 31 175-182 Watkins P & Whitcomb R 1998 Hepatic dysfunction associated with troglitazone N Engl J Med 338 916-917 Wei Y, Sowers J, Nistala R, Gong H, Uptergrove G, Clark S, Morris E, Szary N, Manrique C & Stump C 2006 Angiotensin II-induced NADPH oxidase activation impairs insulin signaling in skeletal muscle cells J Biol Chem 281 35137-35146 Wen Q, Sim MK & Tang FR 2004 Reduction of infarct size by orally administered desaspartate-angiotensin I in the ischemic reperfused rat heart Regul Pept 120 149-153 West D, Boozer C, Moody D & Atkinson R 1992 Dietary obesity in nine inbred mouse strains Am J Physiol 262 R1025-1032 White M 2003 Insulin signaling in health and disease Science 302 1710-1711 White MF & Yenush L 1998 The IRS-signaling system: a network of docking proteins that mediate insulin and cytokine action Curr Top Microbiol Immunol 228 179-208 Wild S, Roglic G, Green A, Sicree R & King H 2004 Global prevalence of diabetes: estimates for the year 2000 and projections for 2030 Diabetes Care 27 1047-1053 Wing R, Blair E, Bononi P, Marcus M, Watanabe R & Bergman R 1994 Caloric restriction per se is a significant factor in improvements in glycemic control and insulin sensitivity during weight loss in obese NIDDM patients Diabetes Care 17 30-36 Wu M, Johnston P, Sheu W, Hollenbeck C, Jeng C, Goldfine I, Chen Y & Reaven G 1990 Effect of metformin on carbohydrate and lipoprotein metabolism in NIDDM patients Diabetes Care 13 1-8 Xu G, Stoffers D, Habener J & Bonner-Weir S 1999 Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats Diabetes 48 2270-2276 167 Yeh T, Sbodio J, Tsun Z, Luo B & Chi N 2007 Insulin-stimulated exocytosis of GLUT4 is enhanced by IRAP and its partner tankyrase Biochem J 402 279-290 Zhang J, Ferguson S, Barak L, Ménard L & Caron M 1996 Dynamin and beta-arrestin reveal distinct mechanisms for G protein-coupled receptor internalization J Biol Chem 271 18302-18305 Zhang J, Hanesworth J, Sardinia M, Alt J, Wright J & Harding J 1999 Structural analysis of angiotensin IV receptor (AT4) from selected bovine tissues J Pharmacol Exp Ther 289 1075-1083 Zhang J, Stobb J, Hanesworth J, Sardinia M & Harding J 1998 Characterization and purification of the bovine adrenal angiotensin IV receptor (AT4) using [125I]benzoylphenylalanine-angiotensin IV as a specific photolabel J Pharmacol Exp Ther 287 416-424 168 ... protein kinase C induces serine phosphorylation of insulin receptor and IRS-1, which inhibits the insulin signalling 14 IRS-1 plays a pivotal role in insulin signalling In its N-terminus, contains... protein kinase C induces serine phosphorylation of insulin receptor and IRS-1, which inhibits the insulin signalling (Figure 1.2) 13 Figure 1.2 Insulin signalling system in skeletal muscle Insulin... NADPH ND Angiotensin converting enzyme Acyl-coenzyme A dehydrogenase Protein kinase B Angiotensin I Angiotensin II Angiotensin III Angiotensin IV One-way analysis of variance Angiotensin receptor