Home >> Current Vascular Pharmacology, Volume 6, Number 4

The Crosstalk Between Insulin and Renin-Angiotensin-Aldosterone Signaling Systems and its Effect on Glucose Metabolism and Diabetes Prevention

Authors: Muscogiuri, Giovanna; Chavez, Alberto O.; Gastaldelli, Amalia; Perego, Lucia; Tripathy, Devjit; Saad, Mario J.; Velloso, Licio; Folli, Franco

Source: Current Vascular Pharmacology, Volume 6, Number 4, October 2008 , pp. 301-312(12)

Publisher: Bentham Science Publishers

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Abstract:

Essential hypertension is an insulin resistant state. Early insulin signaling steps are impaired in essential hypertension and a large body of data suggests that there is a crosstalk at multiple levels between the signal transduction pathways that mediate insulin and angiotensin II actions. At the extracellular level the angiotensin converting enzyme (ACE) regulates the synthesis of angiotensin II and bradykinin that is a powerful vasodilator. At early intracellular level angiotensin II acts on JAK-2/IRS1-IRS2/PI3-kinase, JNK and ERK to phosphorylate serine residues of key elements of insulin signaling pathway therefore inhibiting signaling by the insulin receptor. On another level angiotensin II inhibits the insulin signaling inducing the regulatory protein SOCS 3. Angiotensin II acting through the AT1 receptor can inhibit insulininduced nitric oxide (NO) production by activating ERK 1/2 and JNK and enhances the activity of NADPH oxidase that leads to an increased reactive oxygen species generation. From the clinical standpoint, the inhibition of the renin angiotensin system improves insulin sensitivity and decreases the incidence of Type 2 Diabetes Mellitus (T2DM). This might represent an alternative approach to prevent type 2 diabetes in patients with hypertension and metabolic syndrome, (i.e. insulin resistant patients). This review will discuss: a) the molecular mechanisms of the crosstalk between the insulin and angiotensin II signaling systems b) the results of clinical studies employing drugs targeting the renin-angiotensin IIaldosterone systems and their role in glucose metabolism and diabetes prevention.

More about this publication?
  • Vascular disease is the commonest cause of death in Westernized countries and its incidence is on the increase in developing countries. It follows that considerable research is directed at establishing effective treatment for acute vascular events. Long-term treatment has also received considerable attention (e.g. for symptomatic relief). Furthermore, effective prevention, whether primary or secondary, is backed by the findings of several landmark trials.

    Vascular disease is a complex field with primary care physicians and nurse practitioners as well as several specialties involved. The latter include cardiology, vascular and cardio thoracic surgery, general medicine, radiology, clinical pharmacology and neurology (stroke units). Current Vascular Pharmacology will publish reviews to update all those concerned with the treatment of vascular disease. For example, reviews commenting on recently published trials or new drugs will be included. In addition to clinically relevant topics we will consider 'research-based' reviews dealing with future developments and potential drug targets. Therefore, another function of Current Vascular Pharmacology is to bridge the gap between clinical practice and ongoing research.

    Debates will also be encouraged in the correspondence section of this journal.
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