The renin-angiotensin aldosterone system (RAAS) is well-established to be involved in diabetic nephropathy. Several abnormalities in the RAAS have been described in diabetes mellitus, including an abnormal aldosterone to renin ratio, elevated angiotensin I-converting enzyme (ACE) levels, and altered angiotensin II sensitivity. Whereas the renoprotective properties of ACE-inhibition in diabetic nephropathy have been demonstrated more than a decade ago, somewhat surprisingly, the role of ACE-activity in the pathogenesis of diabetic nephropathy is not well established. This paper addresses the possible functional impact of genetic and environmental increased in ACE activity in the pathogenesis of diabetic renal damage, in the context of the various other abnormalities in the RAAS in diabetes. Human and experimental data on circulating and tissue ACE in diabetes are reviewed, as well as the associations of ACE with angiotensin I conversion, with pathophysiological responses, and with renal end organ damage. New data from our laboratory provide evidence for interaction between genetical regulation of ACE activity by the ACE (I/D) genotype and diabetes as an environmental factor. Moreover, for functional effects of the elevated ACE activity in terms of increased conversion of angiotensin I to angiotensin II. The effects of enhanced generation of angiotensin II are modulated by the angiotensin II-subtype I receptor (AT1R). Altered AT1R sensitivity has been reported in diabetes that may further modulate the eventual effects of elevated ACE. Epidemiological data on the association of genetically elevated ACE activity with diabetic nephropathy provide support for a pathogenetic role of elevated ACE activity in diabetic nephropathy. Together, the data suggest that differences in ACE expression and activity, resulting from both genetic and environmental factors and their interaction can modulate the pathogenesis of diabetic nephropathy. Unravelling the nature of this interaction, with focus on modifiable environmental factors, may help to ameliorate the risk for nephropathy in diabetes.
Keywords: RAAS, ACE, Diabetes, ACE genotype
Pharmacology and Perioperative Considerations for Diabetes Mellitus Medications
Current Clinical Pharmacology Neck Circumference and its Correlation to Other Anthropometric Parameters and Finnish Diabetes Risk Score (FINDRISC)
Current Diabetes Reviews Cardiovascular Diseases and the Nitric Oxide Pathway
Current Vascular Pharmacology Structure – Function Relationships of Pre-Fibrillar Protein Assemblies in Alzheimers Disease and Related Disorders
Current Alzheimer Research Traditional Cardiovascular Risk Factors in Adolescents with Type 1 Diabetes Mellitus
Current Diabetes Reviews In Vivo Bioluminescence Imaging to Assess Pancreatic Islets
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents GLP-1 Agonists and Satiety
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization) Co-morbidity of Diabetes Mellitus and Orodental Diseases in Nigeria
Current Diabetes Reviews Visfatin: Structure, Function and Relation to Diabetes Mellitus and Other Dysfunctions
Current Medicinal Chemistry Diabetes Mellitus to Neurodegenerative Disorders: Is Oxidative Stress Fueling the Flame?
CNS & Neurological Disorders - Drug Targets Gut Microbiota as a Therapeutic Target for Metabolic Disorders
Current Medicinal Chemistry Novel Peptides under Development for the Treatment of Type 1 and Type 2 Diabetes Mellitus
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Irbesartan and Hydrochlorothiazide Association in the Treatment of Hypertension
Current Vascular Pharmacology Survey of Mortality Due to Influenza A in North of Iran, 2015-2016
Current Respiratory Medicine Reviews Update on the Protective Renal Effects of Metformin in Diabetic Nephropathy
Current Medicinal Chemistry DGAT: Novel Therapeutic Target for Obesity and Type 2 Diabetes Mellitus
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Update on Pharmacologic Approaches to Prevent Thromboembolism in Atrial Fibrillation: Are Thrombin and Factor Xa Inhibitors the Ultimate Answer?
Current Vascular Pharmacology Editorial [Hot Topic: Management of Diabetes Mellitus: The Five Pillars of Wisdom (Guest Editors: C.D.A. Stehouwer, N.C. Schaper and M. Huijberts)]
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization) Clopidogrel in Secondary Ischemic Stroke Prevention
Recent Patents on Cardiovascular Drug Discovery (Discontinued) Effects of Mesenchymal Stromal Cells on Diabetic Cardiomyopathy
Current Pharmaceutical Design