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This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/E802    most recent 00650.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Müller, H. Articles by Raasch, W. Search for Related Content PubMed PubMed Citation Articles by Müller, H. Articles by Raasch, W.

Angiotensin II stimulates the reactivity of the pituitary-adrenal axis in leptin-resistant Zucker rats, thereby influencing the glucose utilization

Institute of Experimental and Clinical Pharmacology and Toxicology, University Clinic of Schleswig-Holstein, Lübeck, Germany

Submitted 29 November 2006 ; accepted in final form 21 June 2007

The HPA axis is hyperactive under conditions of leptin and insulin resistance as well as after ANG II administration. We hypothesized that a hyperreactivity of the HPA axis to ANG contributes to an impaired glucose utilization in obesity, since leptin resistance and an overactive renin-angiotensin-aldosterone system are features of obesity. Zucker rats were treated with ANG via subcutaneous minipumps (0, 0.9, and 9.0 µg/h; 4 wk). PA axis reactivity and glucose homeostasis were characterized after CRH treatment and during an oral glucose tolerance test (OGTT). The elevated plasma profile of corticosterone after CRH stimulation in saline-treated OZR compared with LZR confirmed that the sensitization of the PA axis depended on leptin resistance. Irrespective of the rat strain, circulating ANG levels and blood pressure were selectively increased after administration of 9 µg/h ANG (high ANG). Only high ANG induced an elevation of the corticosterone and glucose response after CRH stimulation in OZR but did not affect the ACTH secretion. During OGTT, corticosterone and consequently glucose increased in OZR after high ANG, whereas the insulin secretion was decreased. In the adrenal glands of OZR, AT_1A receptor mRNA levels increased after high ANG. We conclude that the impairment of glucose utilization after ANG stimulation is potentiated in leptin-resistant rats as a result of a hyperreactive PA axis, thereby confirming the functional importance of a dysregulation within the HPA axis in metabolic syndrome or obesity. The ACTH-independent stimulation of corticosterone release and the selective increase of AT_1A receptor mRNA in the adrenals of OZR indicated a sensitization of adrenals toward ANG, causing a stimulation of the PA axis.

renin-angiotensin-aldosterone system; obesity; corticosterone; adrenocorticotropic hormone; diabetes