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Thirty-six male Zucker diabetic fatty (ZDF) rats, 10 weeks of age, were randomized to receive the angiotensin-converting enzyme inhibitor perindopril (8 mg\/l in drinking water; n = 12), irbesartan (15 mg\/kg via gavage; n = 12), or no treatment (n = 12) for 10 weeks. Results were compared with lean littermates (ZL) (n = 12) studied concurrently. ZDF rats had increased intra-islet expression of components of the RAS correlating with increased intraislet fibrosis, apoptosis, and oxidative stress. Disordered islet architecture, seen in ZDF rats, was attenuated after treatment with perindopril or irbesartan. Islet fibrogenesis was also diminished, as measured by picrosirius staining and expression of collagens I and IV. Gene expression of transforming growth factor-\u03b21 was increased in the ZDF pancreas (ZL, 1.0 \u00b1 0.1; ZDF, 2.0 \u00b1 0.3; P &amp;lt; 0.05) and reduced after blockade of the RAS (ZDF + P, 1.3 \u00b1 0.2; ZDF + I, 1.5 \u00b1 0.1; vs. ZDF, both P &amp;lt; 0.05). Improvements in structural parameters were also associated with functional improvements in first-phase insulin secretion. These findings provide a possible mechanism for the reduced incidence of new-onset diabetes that has been observed in clinical trials of RAS blockade.<\/jats:p>","DOI":"10.2337\/diabetes.53.4.989","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"989-997","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":230,"title":["Improved Islet Morphology after Blockade of the Renin- Angiotensin System in the ZDF Rat"],"prefix":"10.2337","volume":"53","author":[{"given":"Christos","family":"Tikellis","sequence":"first","affiliation":[{"name":"Danielle Alberti Memorial Centre for Diabetic Complications, Baker Medical Research Institute, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Wookey","sequence":"additional","affiliation":[{"name":"Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Candido","sequence":"additional","affiliation":[{"name":"Danielle Alberti Memorial Centre for Diabetic Complications, Baker Medical Research Institute, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sof","family":"Andrikopoulos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merlin C.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Danielle Alberti Memorial Centre for Diabetic Complications, Baker Medical Research Institute, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Danielle Alberti Memorial Centre for Diabetic Complications, Baker Medical Research Institute, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031217020401700_R1","doi-asserted-by":"crossref","unstructured":"Danser AH: Local renin-angiotensin systems: the unanswered questions. 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