title: Modulation of glucose metabolism by the renin-angiotensin-aldosterone system.
abstract: The renin-angiotensin-aldosterone system (RAAS) is an enzymatic cascade functioning in a paracrine and autocrine fashion. In animals and humans, RAAS intrinsic to tissues modulates food intake, metabolic rate, adiposity, insulin sensitivity, and insulin secretion. A large array of observations shows that dysregulation of RAAS in the metabolic syndrome favors type 2 diabetes. Remarkably, angiotensin-converting enzyme inhibitors, suppressing the synthesis of angiotensin II (ANG II), and angiotensin receptor blockers, targeting the ANG II type 1 receptor, prevent diabetes in patients with hypertensive or ischemic cardiopathy. These drugs interrupt the negative feedback loop of ANG II on the RAAS cascade, which results in increased production of angiotensins. In addition, they change the tissue expression of RAAS components. Therefore, the concept of a dual axis of RAAS regarding glucose homeostasis has emerged. The RAAS deleterious axis increases the production of inflammatory cytokines and raises oxidative stress, exacerbating the insulin resistance and decreasing insulin secretion. The beneficial axis promotes adipogenesis, blocks the production of inflammatory cytokines, and lowers oxidative stress, thereby improving insulin sensitivity and secretion. Currently, drugs targeting RAAS are not given for the purpose of preventing diabetes in humans. However, we anticipate that in the near future the discovery of novel means to modulate the RAAS beneficial axis will result in a decisive therapeutic breakthrough.
authors.affiliation: Institut National de la Sante et de la Recherche Medicale, U 1081, Institute for Research on Cancer and Aging of Nice (IRCAN), "Aging and Diabetes" Team, Nice, France; Centre National de la Recherche Scientifique, UMR7284, IRCAN, Nice, France; University of Nice-Sophia Antipolis, Nice, France; Nephrology Department, University Hospital, Nice, France; and favre@unice.fr.
authors.forename: Guillaume A
authors.initials: GA
authors.lastname: Favre
authors.affiliation: Institut National de la Sante et de la Recherche Medicale, U 1081, Institute for Research on Cancer and Aging of Nice (IRCAN), "Aging and Diabetes" Team, Nice, France; Centre National de la Recherche Scientifique, UMR7284, IRCAN, Nice, France; University of Nice-Sophia Antipolis, Nice, France; Nephrology Department, University Hospital, Nice, France; and.
authors.forename: Vincent L M
authors.initials: VL
authors.lastname: Esnault
authors.affiliation: Institut National de la Sante et de la Recherche Medicale, U 1081, Institute for Research on Cancer and Aging of Nice (IRCAN), "Aging and Diabetes" Team, Nice, France; Centre National de la Recherche Scientifique, UMR7284, IRCAN, Nice, France; University of Nice-Sophia Antipolis, Nice, France; Clinical Chemistry Laboratory, University Hospital, Nice, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Van Obberghen
mesh_terms: D050156:Adipogenesis / Q000502:physiology; D050154:Adiposity / Q000502:physiology; D000450:Aldosterone / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D050155:Lipogenesis / Q000502:physiology; D008969:Molecular Sequence Data; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D000450:Aldosterone; D005947:Glucose
keywords: insulin resistance; insulin target tissues; obesity; renin-angiotensin-aldosterone system; white adipose tissue