Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the study was to identify pancreatic stellate cells (PSCs) as a potential target of angiotensin II (ATII) action because recently a local renin-angiotensin system (RAS) has been described in the pancreas. PSCs were isolated from male Wistar rats and investigated for ATII receptor expression and ATII-induced calcium transients, contractions, proliferation, and alpha-smooth muscle actin expression. Quiescent and activated PSCs expressed the ATII receptor subtype AT1 but not AT2. Addition of ATII led to a rapid elevation of intracellular calcium ([Ca]i). The sensitivity toward ATII with respect to calcium transients did not change during the transdifferentiation process. In activated PSCs, ATII dose dependently induced PSC cell contraction. Furthermore, ATII induced an activation of the c-Jun-N-terminal kinase (JNK) and extracellular regulated kinase (Erk), which was inhibited after intracellular calcium chelation by BAPTA-AM. The p38 mitogen-activated protein kinase (p38) was also activated by ATII. BAPTA-AM itself induced p38 activation, which was not further enhanced by ATII. ATII stimulated PSC proliferation, while PSC transdifferentiation, as indicated by alpha-smooth muscle actin expression and collagen type I secretion, was not enhanced. The data suggest that PSCs are targets of ATII action with potential pathophysiological relevance.
Pancreas 2004 Mar
PMID:Effects of angiotensin II on rat pancreatic stellate cells. 1502 44

Several regulatory systems are implicated in the regulation of islet function and beta cell mass. Of great interest in this context are some endocrine, paracrine/autocrine, and intracrine regulators. These include, to name but a few, the gut peptides, growth factors, prostaglandins, and some vasoactive mediators such as nitric oxide, bradykinins, endothelins, and angiotensins. Apart from its potent vasoconstrictor actions, the renin-angiotensin system (RAS) that generates angiotensin II has several novel functions-stimulation and inhibition of cell proliferation; induction of apoptosis; generation of reactive oxygen species; regulation of hormone secretion; and proinflammatory and profibrogenic actions. In the pancreas, recent evidence supports the presence of an islet RAS, which is subject to activation by islet transplantation and diabetes. Such a local islet RAS, if activated, may drive islet fibrosis and reduce islet blood flow, oxygen tension, and insulin biosynthesis. Moreover, activation of an islet RAS may drive the synthesis of reactive oxygen species, cause oxidative stress-induced beta cell dysfunction and apoptosis, and thus contribute to the islet dysfunction seen in type 2 diabetes and after islet transplantation. Blockade of the RAS could contribute to the development of novel therapeutic strategies in the prevention and treatment of patients with diabetes and in islet transplantation.
Pancreas 2005 May
PMID:Pancreatic islet renin angiotensin system: its novel roles in islet function and in diabetes mellitus. 1584 Oct 36

The renin-angiotensin system (RAS) is altered in diabetes. The aim of our study was to investigate whether streptozotocin-induced diabetes was associated with a change in angiotensin II receptors AT (1) and angiotensin-converting enzyme (ACE) mRNA expression in the pancreas in vivo. Rats were synchronized to a 12:12 light:dark cycle. Pancreas tissue sampling was done at 4 h intervals during 24 h cycle starting 17 days after streptozotocin (STZ) treatment (65 mg/kg of body weight). Real time PCR showed decreased expression of ACE in the pancreas after STZ administration during the dark phase. Expression of AT (1) was decreased in diabetic rats during the light and the dark phase of 24 h cycle. Our data show down-regulation of the pancreatic RAS during early stage of diabetes development.
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PMID:Down regulation of angiotensin II receptor AT1 expression in the pancreas of diabetic rat. 1947

Type 1 diabetes is a T-cell mediated autoimmune disease characterized by pancreatic beta cells destruction. Angiotensin-converting enzyme 2 (ACE2), a component of renin-angiotensin system (RAS) has been identified in pancreas from type 2 diabetic mice and its overexpression prevents beta cell dysfunction. We studied the effect of ACE2 deletion on pancreatic and renal function in the nonobese diabetic mice, a model that mimics type 1 diabetes. ACE2-deficient NOD mice and the respective controls were generated. Pancreas function and immunohistochemistry studies were performed. Renal function and RAS gene expression were also analyzed. Renal proximal tubular cells were obtained from these animals to dissect the effect of ACE2 deficiency in these cells. In NOD mice, ACE2 deletion significantly worsened glucose homeostasis, decreased islet insulin content, increased beta cell oxidative stress, and RIPK1-positive islets as compared with control mice. Angiotensin-converting enzyme and angiotensin II type 1 receptor (AT1R) were also increased in ACE2-deficient mice. In kidneys of 30-day diabetic mice, ACE2 deletion decreased podocyte number within the glomeruli, and altered renal RAS gene expression in tubules. ACE2 deletion influenced the expression of fibrosis-related genes in isolated primary renal proximal tubular cells before diabetes onset in NOD mice. Our findings suggest that ACE2 deletion may have a deleterious impact on beta cell and renal function, by promoting oxidative stress and increasing necroptosis mediators. In addition, this effect is accompanied by RAS alterations in both pancreas and renal proximal tubular cells, indicating that ACE2 may exert a renopancreatic protective effect on type 1 diabetes, which is activated before diabetes starts.
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PMID:Angiotensin-converting enzyme 2 influences pancreatic and renal function in diabetic mice. 3247 97