The direct effects of the angiotensin-converting enzyme inhibitors, zofenoprilat and enalaprilat, on isolated human pancreatic islets.

Content Provider	Semantic Scholar
Author	Guerra, Silvia Del Bugliani, Marco Boggi, Ugo Mosca, Franco Torri, Scilla Prato, Stefano Del Marchetti, Piero
Copyright Year	2006
Abstract	OBJECTIVE Data from prospective studies suggest a significant reduction in the risk of new diabetes from drug therapies containing angiotensin-converting enzyme (ACE) inhibitors. Since the renin-angiotensin system (RAS) has been found locally in several tissues and cells, including pancreatic islets, we hypothesized that the positive metabolic effects of ACE inhibitors may be due to a beneficial action of these compounds on insulin-secreting beta-cells. DESIGN AND METHODS Isolated human pancreatic islets were studied after 24 h of incubation with 22.2 mmol/l glucose, with or without the presence in the incubation medium of 0.5-6.0 mmol/l zofenoprilat or enalaprilat, ACE inhibitor drugs which differ by the presence of a sulphydryl or a carboxyl group in their structural formula. Functional and molecular studies were then performed to assess insulin secretion, redox balance, mRNA and protein expression. RESULTS Angiotensinogen, ACE and angiotensin type 1 receptor mRNA expression increased in islets cultured in high glucose; this was similarly prevented by the presence of either ACE inhibitor. As expected, preculture of human islets in high glucose determined a marked reduction in insulin secretion which was associated with enhanced oxidative stress, as shown by increased nitrotyrosine concentrations, and enhanced expression of protein kinase C beta and NADPH oxidase. The presence of either of the ACE inhibitors counteracted several of the deleterious effects of high glucose exposure, including reduction of insulin secretion and increased oxidative stress; zofenoprilat showed significantly more marked effects. CONCLUSIONS These results showed that: (a) RAS molecules are present in human islets and their expression is sensitive to glucose concentration, (b) ACE inhibitors, and in particular zofenoprilat, protect human islets from glucotoxicity and (c) the effects of ACE inhibition are associated with decreased oxidative stress. Together, these findings provide evidence that the possible beneficial effects of ACE inhibitors in human diabetes are due, at least in part, to a protective action on pancreatic beta-cells.
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Alternate Webpage(s)	https://eje.bioscientifica.com/downloadpdf/journals/eje/154/2/1540355.pdf
Alternate Webpage(s)	http://www.eje-online.org/content/154/2/355.full.pdf
PubMed reference number	16452552v1
Volume Number	154
Issue Number	2
Journal	European journal of endocrinology
Language	English
Access Restriction	Open
Subject Keyword	3-nitrotyrosine Angiotensin-Converting Enzyme Inhibitors Angiotensinogen Angiotensins Body tissue Carboxyl Group Cell secretion Diabetes Mellitus Enalaprilat Glucose Islets of Langerhans NADPH Oxidase Oxidative Stress Pharmacotherapy Protein Kinases Receptor, Angiotensin, Type 1 Renin-angiotensin system Sulfhydryl Compounds insulin secretion protein expression zofenoprilate
Content Type	Text
Resource Type	Article