diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/2072-0351-5481diaendo-5481Research ArticleСтатьиArticlesРоль тканевой ренин-ангиотензин-альдостероновой системы в развитии метаболического синдрома, сахарного диабета и его сосудистых осложненийThe role of the tissue renin-angiotensin-aldosterone system in the development of metabolic syndrome, diabetes mellitus and itsvascular complicationsШестаковаМарина ВладимировнаShestakovaMarina Vladimirovnanephro@endocrincentr.ruФГУ Эндокринологический научный центр, МоскваEndocrinology Research Centre, Moscow201015092010133№3 (2010)1419Copyright © Шестакова М.В., 20102010Шестакова М.В.Shestakova M.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/5481

Ренин-ангиотензин-альдостероновая система (РААС) - одна из ключевых систем организма человека, имеющая первостепенное значениев регуляции большинства физиологических и патофизиологических состояний: тонуса сосудов и уровня АД, ремоделирования сосудистойстенки и сердечной мышцы, механизмов развития и прогрессирования атеросклероза, гломерулосклероза и других патологий. Принци-пиальным открытием конца ХХ века является обнаружение локальных (тканевых) РААС, т.е. открытие синтеза всех компонентовэтой системы (от ренина до альдостерона) непосредственно в тканях и органах-мишенях. Именно активация тканевых РААС играетведущую роль в развитии сосудистых осложнений сахарного диабета (СД): сердечно-сосудистой патологии, диабетической нефропатии(ДН) и ретинопатии. Исследования последних лет позволили обнаружить компоненты РААС локально в жировой ткани, в поджелудочнойжелезе. Доказана роль этой системы в развитии висцерального ожирения, предиабета и самого СД 2 типа (СД2). Эти данные подтвер-ждаются снижением риска развития СД2 на фоне длительного лечения блокаторами РААС.

Renin-angiotensin-aldosterone system (RAAS) is a major system of the human body playing a key role in the regulation of most physiological andpathological conditions, such as vascular tone, AD level, myocardial and vascular wall remodeling, development of atherosclerosis, glomerulosclerosis,and other pathologies. The discovery of local (tissue) RAAS in the late XX century gave evidence of direct synthesis of all components of this system,from renin to aldosterone, in target tissues and organs. Activation of tissue RAAS was shown to play a leading role in the evolvement of diabetic complicationsincluding cardiovascular diseases, diabetic nephropathy (DN), and retinopathy. Recent studies revealed the presence of RAAS componentsin fat and pancreas. This system is involved in the development of visceral obesity, pre-diabetes, and Type 2 diabetes. These findings are confirmedby a reduced risk of CDM2 in subjects receiving long-term therapy with RAAS blockers.

ренин-ангиотензин-альдостероновая системависцеральное ожирениеметаболический синдромсахарный диабетдиабетическая нефропатиядиабетическая ретинопатияrenin-angiotensin-aldosterone systemvisceral obesitymetabolic syndromediabetes mellitusdiabetic nephropathydiabetic retinopathyReferencesDihn D.T., Frauman A.G., Jonston C.I., Fabiani M.E. Angiotensin receptors: distribution, signaling and function // Clinical Sci. - 2001. - 100. - Р. 481-492.Dihn D.T., Frauman A.G., Jonston C.I., Fabiani M.E. Angiotensin receptors: distribution, signaling and function // Clinical Sci. - 2001. - 100. - Р. 481-492.Paul M., Mehr A., Kreutz R. Physiology of Local Renin-Angiotensin Systems // Physiol Rev. - 2006. - 86. - Р. 747-803.Paul M., Mehr A., Kreutz R. Physiology of Local Renin-Angiotensin Systems // Physiol Rev. - 2006. - 86. - Р. 747-803.Campbell D.J. The site of angiotensin production // J. Hypertens. - 1985. - 3. - Р. 199-207.Campbell D.J. The site of angiotensin production // J. Hypertens. - 1985. - 3. - Р. 199-207.Rosenberg M.E., Smith L.J., Correa-Rotter R., Hostetter T.H. The paradox of the renin-angiotensin system in chronic renal disease // Kidney Int. - 1994. - 45. - Р. 403-410.Rosenberg M.E., Smith L.J., Correa-Rotter R., Hostetter T.H. The paradox of the renin-angiotensin system in chronic renal disease // Kidney Int. - 1994. - 45. - Р. 403-410.Price D.A., Porter L.E., Gordon M. The Paradox of the Low-Renin State in Diabetic Nephropathy // J. Am. Soc. Nephrol. - 1999. - 10. - Р. 2382-2391.Price D.A., Porter L.E., Gordon M. The Paradox of the Low-Renin State in Diabetic Nephropathy // J. Am. Soc. Nephrol. - 1999. - 10. - Р. 2382-2391.Bojestig M., Nystrom F., Arnqvist HJ., et al. The renin-angiotensin-aldosteron system is suppressed in adults with type 1 diabetes // JRAAS. - 2000. - 1. - Р. 353-356.Bojestig M., Nystrom F., Arnqvist HJ., et al. The renin-angiotensin-aldosteron system is suppressed in adults with type 1 diabetes // JRAAS. - 2000. - 1. - Р. 353-356.Kang J.J., Toma I., Sipos A. et al. The collecting duct is the major source of prorenin in diabetes // Hypertension. - 2008. - 51. - Р. 1597- 1604.Kang J.J., Toma I., Sipos A. et al. The collecting duct is the major source of prorenin in diabetes // Hypertension. - 2008. - 51. - Р. 1597- 1604.Shiigai T., Shichiri M. Late escape from the antiproteinuric effect of ACE inhibitors in nondiabetic renal disease // Am. J. Kidney Dis. - 2001. - 37. - Р. 477-483.Shiigai T., Shichiri M. Late escape from the antiproteinuric effect of ACE inhibitors in nondiabetic renal disease // Am. J. Kidney Dis. - 2001. - 37. - Р. 477-483.Шамхалова М.Ш., Трубицына Н.П., Шестакова М.В. Феномен ча- стичного ускользания блокады ангиотензин АТ II у больных сахарным диабетом типа 2 и диабетической нефропатией. Тер. арх. - 2008. - 1. - С. 49-52.Шамхалова М.Ш., Трубицына Н.П., Шестакова М.В. Феномен ча- стичного ускользания блокады ангиотензин АТ II у больных сахарным диабетом типа 2 и диабетической нефропатией. Тер. арх. - 2008. - 1. - С. 49-52.Wolf G., Butzmann U., Wenzel U.O. The rennin-angitensin system and progression of renal disease: from hemodynamics to cell biology // Nephron Physiol. - 2003. - 93. - Р. 3-13.Wolf G., Butzmann U., Wenzel U.O. The rennin-angitensin system and progression of renal disease: from hemodynamics to cell biology // Nephron Physiol. - 2003. - 93. - Р. 3-13.Wagner J., Danser A.H.J., Derkx F.H. et al. Demonstration of renin mRNA, angiotensinogen mRNA, and angiotensin converting enzyme mRNA expression in the human eye: evidence for an intraocular reninangiotensin system // Br. J. Ophthalmol. - 1996. - 80. - Р. 159- 163.Wagner J., Danser A.H.J., Derkx F.H. et al. Demonstration of renin mRNA, angiotensinogen mRNA, and angiotensin converting enzyme mRNA expression in the human eye: evidence for an intraocular reninangiotensin system // Br. J. Ophthalmol. - 1996. - 80. - Р. 159- 163.Murata M., Nakagawa M., Takahashi S. Expression and localisation of angiotensin II type 1 receptor mRNA in rat ocular tissues // Ophtalmologica. - 1997. - 211. - Р. 384-386.Murata M., Nakagawa M., Takahashi S. Expression and localisation of angiotensin II type 1 receptor mRNA in rat ocular tissues // Ophtalmologica. - 1997. - 211. - Р. 384-386.Danser A.H.J., Derkx F.H., Admiraal P.J.J. et al. Angiotensin levels in the eye // Invest Ophtalmol Vis Sci. - 1994. - 35. - Р. 1008-1018.Danser A.H.J., Derkx F.H., Admiraal P.J.J. et al. Angiotensin levels in the eye // Invest Ophtalmol Vis Sci. - 1994. - 35. - Р. 1008-1018.Stain W.D., Chaturvedi N. Review: the rennin-angiotensin-aldosterone system and the eye in diabetes // JRAAS. - 2002. - 3. - Р. 243-246.Stain W.D., Chaturvedi N. Review: the rennin-angiotensin-aldosterone system and the eye in diabetes // JRAAS. - 2002. - 3. - Р. 243-246.Shweiki D., Itin A., Soffer D., Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenes // Nature. - 1992. - 359. - Р. 843-845.Shweiki D., Itin A., Soffer D., Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenes // Nature. - 1992. - 359. - Р. 843-845.Natarajan R., Bai W., Lanting L. et al. Effects of high glucose on vascular endothelial growth factor expression in vascular smooth muscle cells // Am. J. Physiol. - 1997. - 273. - H2224-H2231.Natarajan R., Bai W., Lanting L. et al. Effects of high glucose on vascular endothelial growth factor expression in vascular smooth muscle cells // Am. J. Physiol. - 1997. - 273. - H2224-H2231.Williams B., Baker A.Q., Gallacher B. et al. Angiotensin II increases vascular permeability factor gene expression by human vascular smooth muscle cells.Williams B., Baker A.Q., Gallacher B. et al. Angiotensin II increases vascular permeability factor gene expression by human vascular smooth muscle cells.Otani A., Takagi H., Oh H. et al. Angiotensin II Induces Expression of the Tie2 Receptor Ligand, Angiopoietin-2, in Bovine Retinal Endothelial Cells // Diabetes. - 2001. - 50 . - Р. 867-875.Otani A., Takagi H., Oh H. et al. Angiotensin II Induces Expression of the Tie2 Receptor Ligand, Angiopoietin-2, in Bovine Retinal Endothelial Cells // Diabetes. - 2001. - 50 . - Р. 867-875.Funatsu H., Yamashita H., Nakanishi Y., et al. Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy // Br. J. Ophthalmol. - 2002. - 86. - Р. 311-315.Funatsu H., Yamashita H., Nakanishi Y., et al. Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy // Br. J. Ophthalmol. - 2002. - 86. - Р. 311-315.Chaturverdi N., Sjolie A.K., Stephenson J.M. et al. Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes // Lancet. - 1998. - 351. - Р. 28-31.Chaturverdi N., Sjolie A.K., Stephenson J.M. et al. Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes // Lancet. - 1998. - 351. - Р. 28-31.Sjїlie A.K., Klein R., Porta M., Orchard T., Fuller J., Parving H.H. et al. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo controlled trial // Lancet. - 2008. - 372. - Р. 1385-1393.Sjїlie A.K., Klein R., Porta M., Orchard T., Fuller J., Parving H.H. et al. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo controlled trial // Lancet. - 2008. - 372. - Р. 1385-1393.Lindpaintner K., Jin M., Wilhelm M.J. et al. Intracardiac generation of angiotensin and its physiologic role // Circulation. - 1988. - 77 (suppl.1). - Р. 18-23.Lindpaintner K., Jin M., Wilhelm M.J. et al. Intracardiac generation of angiotensin and its physiologic role // Circulation. - 1988. - 77 (suppl.1). - Р. 18-23.Bader M. Tissue rennin-angiotensin-aldosterone systems: targets for pharmacological therapy // Annu Review Pharm Toxicol. - 2010. - 50. - Р. 439-465.Bader M. Tissue rennin-angiotensin-aldosterone systems: targets for pharmacological therapy // Annu Review Pharm Toxicol. - 2010. - 50. - Р. 439-465.Hoshida S., Kato J., Nishino M. Et al. Increased Angiotensin-Converting Enzyme Activity in Coronary Artery Specimens From Patients With Acute Coronary Syndrome // Circulation. - 2001. - 103. - Р. 630- 638.Hoshida S., Kato J., Nishino M. Et al. Increased Angiotensin-Converting Enzyme Activity in Coronary Artery Specimens From Patients With Acute Coronary Syndrome // Circulation. - 2001. - 103. - Р. 630- 638.Sun Y., Weber K.T. RAS and connective tissue in the heart // Int. J. Biochem Cell Biol. - 2003. - 35. - Р. 919-931.Sun Y., Weber K.T. RAS and connective tissue in the heart // Int. J. Biochem Cell Biol. - 2003. - 35. - Р. 919-931.Satoh M., Nakamura M., Saitoh H. et al. Aldosterone sunthase (CYP11B2) expression and myocardial fibrosis in the failing human heart // Clin Sci. - 2002. - 102. - Р. 381-386.Satoh M., Nakamura M., Saitoh H. et al. Aldosterone sunthase (CYP11B2) expression and myocardial fibrosis in the failing human heart // Clin Sci. - 2002. - 102. - Р. 381-386.Pitt B., Zannad F., Remme W.J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure // N. Engl. J. Med. - 1999. - 341. - Р. 709-717.Pitt B., Zannad F., Remme W.J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure // N. Engl. J. Med. - 1999. - 341. - Р. 709-717.Pitt B., Remme W., Zannad F., Neaton J., Martinez F., Roniker B., Bittman R., Hurley S., Kleiman J., Gatlin M. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction // N. Engl. J. Med. - 2003. - 348. - Р. 1309-1321.Pitt B., Remme W., Zannad F., Neaton J., Martinez F., Roniker B., Bittman R., Hurley S., Kleiman J., Gatlin M. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction // N. Engl. J. Med. - 2003. - 348. - Р. 1309-1321.Tahmasebi M., Puddefoot J.R., Inwang E.R., et al. The tissue rennin-angiotensin system in human pancreas // J. Endocrinol. - 1999. - 161. - Р. 317-322.Tahmasebi M., Puddefoot J.R., Inwang E.R., et al. The tissue rennin-angiotensin system in human pancreas // J. Endocrinol. - 1999. - 161. - Р. 317-322.Lam K.Y., Leung P.S. Regulation and expression of rennin-angiotensin system in human pancreas and pancreatic endocrine tumors // Eur. J. Endocrinol. - 2002. - 146. - Р. 567-572.Lam K.Y., Leung P.S. Regulation and expression of rennin-angiotensin system in human pancreas and pancreatic endocrine tumors // Eur. J. Endocrinol. - 2002. - 146. - Р. 567-572.Leung P.S. The physiology of a local renin-angiotensin system in the pancreas // J. Physiol. - 2007. - 580. - Р. 31-37.Leung P.S. The physiology of a local renin-angiotensin system in the pancreas // J. Physiol. - 2007. - 580. - Р. 31-37.Lau T., Carlsson P.O., Leung P.S. Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets // Diabetologia. - 2004. - 47. - Р. 240-248.Lau T., Carlsson P.O., Leung P.S. Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets // Diabetologia. - 2004. - 47. - Р. 240-248.Folli F., Saad M.J.A., Velloso L., et al. Crosstalk between insulin and angiotensin II signaling systems // Exp. Clin. Endocrinol. Diabetes. - 1999. - 107. - Р. 133-139.Folli F., Saad M.J.A., Velloso L., et al. Crosstalk between insulin and angiotensin II signaling systems // Exp. Clin. Endocrinol. Diabetes. - 1999. - 107. - Р. 133-139.Andraws R., Brown D.L. Effect of inhibition of the renin-angiotensin system on development of type 2 diabetes mellitus (meta-analysis of randomized trials) // Am. J. Cardiol. - 2007. - 99. - Р. 1006- 1012.Andraws R., Brown D.L. Effect of inhibition of the renin-angiotensin system on development of type 2 diabetes mellitus (meta-analysis of randomized trials) // Am. J. Cardiol. - 2007. - 99. - Р. 1006- 1012.Whaley-Connell A., Johnson M.S., Sowers J.R. Aldosterone: role in the cardiometabolic syndrome and resistant hypertension // Prog Cardiovasc Dis. - 2010. - 52. - Р. 401-409.Whaley-Connell A., Johnson M.S., Sowers J.R. Aldosterone: role in the cardiometabolic syndrome and resistant hypertension // Prog Cardiovasc Dis. - 2010. - 52. - Р. 401-409.Sharma A.M., Janke J., Gorzelniak K. et al. Angiotensin Blockade Prevents Type 2 Diabetes by Formation of Fat Cells // Hypertension. - 2002. - 40. - Р. 609-612.Sharma A.M., Janke J., Gorzelniak K. et al. Angiotensin Blockade Prevents Type 2 Diabetes by Formation of Fat Cells // Hypertension. - 2002. - 40. - Р. 609-612.Furuhashi M., Ura N., Takizawa H., Yoshida D. et al. Blockade of the renin-angiotensin system decreases adipocyte size with improvement in insulin sensitivity // J. Hypertens. - 2004. - 22. - Р. 1977-1982.Furuhashi M., Ura N., Takizawa H., Yoshida D. et al. Blockade of the renin-angiotensin system decreases adipocyte size with improvement in insulin sensitivity // J. Hypertens. - 2004. - 22. - Р. 1977-1982.Kraus D., Jдger J., Meier B. et al. Aldosterone Inhibits Uncoupling Protein− 1, Induces Insulin Resistance, and Stimulates Proinflammatory Adipokines in Adipocytes // Horm. Metab. Res. - 2005. - 37. - Р. 455-459.Kraus D., Jдger J., Meier B. et al. Aldosterone Inhibits Uncoupling Protein− 1, Induces Insulin Resistance, and Stimulates Proinflammatory Adipokines in Adipocytes // Horm. Metab. Res. - 2005. - 37. - Р. 455-459.Ingelsson E., Pencina M.J., Tofler G.H., et al. Multimarker approach to evaluate the incidence of the metabolic syndrome and longitudinal changes in metabolic risk factors: the Framingham offspring study // Circulation. - 2007. - 116. - Р. 984-992.Ingelsson E., Pencina M.J., Tofler G.H., et al. Multimarker approach to evaluate the incidence of the metabolic syndrome and longitudinal changes in metabolic risk factors: the Framingham offspring study // Circulation. - 2007. - 116. - Р. 984-992.Jeon J.H., Kim K., Kim J.H. et al. A novel adipokine CTRP1 stimulates aldosterone production // The FASEB Journal. - 2008. - 22. - Р. 1502- 1511.Jeon J.H., Kim K., Kim J.H. et al. A novel adipokine CTRP1 stimulates aldosterone production // The FASEB Journal. - 2008. - 22. - Р. 1502- 1511.Lastra-Lastra G., Sowers J.R., Restrepo-Erazo C. et al. Role of Aldosterone and angiotensin II in Insulin Resistance: An Update // Clin. Endocrinol. - 2009. - 71. - Р. 1-6.Lastra-Lastra G., Sowers J.R., Restrepo-Erazo C. et al. Role of Aldosterone and angiotensin II in Insulin Resistance: An Update // Clin. Endocrinol. - 2009. - 71. - Р. 1-6.

The authors declare that there are no conflicts of interest present.