title: Angiotensin converting enzyme 2: a new important player in the regulation of glycemia.
abstract: In spite of the novel antidiabetic drugs available on the market, type 2 diabetes mellitus (T2DM) affects nearly 25 million people in the USA and causes about 5% of all deaths globally each year. Given the rate and proportion by which T2DM is affecting human beings, it is indispensable to identify new therapeutic targets that can control the disease. Recent preclinical and clinical studies suggest that attenuating the activity of the renin-angiotensin system (RAS) could improve glycemia in diabetic patients. Angiotensin-converting enzyme 2 (ACE2) counteracts RAS overactivity by degrading angiotensin-II (Ang-II), a vasoconstrictor, to Ang-(1-7) which is a vasodilator. A decrease in ACE2 and an increase in A disintegrin and metalloproteinase (ADAM17)-mediated shedding activity have been observed with the progression of T2DM, suggesting the importance of this mechanism in the disease. Indeed, restoration of ACE2 improves glycemia in db/db and Ang-II-infused mice. The beneficial effects of ACE2 can be attributed to reduced oxidative stress and ADAM17 expression in the islets of Langerhans in addition to the improvement of blood flow to the β-cells. The advantage of ACE2 over other RAS blockers is that ACE2 not only counteracts the negative effects of Ang-II but also increases Ang-(1-7)/Mas receptor (MasR) [a receptor through which Ang-(1-7) produces its actions] signaling in the cells. Increased Ang-(1-7)/MasR signaling has been reported to improve insulin sensitivity and glycemia in diabetic animals. Altogether, ACE2/Ang-(1-7)/MasR axis of the RAS appears to be protective in T2DM and strategies to restore ACE2 levels in the disease seem to be a promising therapy for Ang-II-mediated T2DM.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Kavaljit H
authors.initials: KH
authors.lastname: Chhabra
authors.forename: Harshita
authors.initials: H
authors.lastname: Chodavarapu
authors.forename: Eric
authors.initials: E
authors.lastname: Lazartigues
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology; D006706:Homeostasis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D012084:Renin-Angiotensin System
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D007004:Hypoglycemic Agents; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2
keywords: A disintegrin, and metalloproteinase (ADAM17); MasR; Type 2 diabetes; angiotensin (1-7); angiotensin converting enyzme 2
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