Angiotensinogen localization and secretion in the rat pancreas

Regoli, Marì; Bendayan, Moı̈se; Fonzi, L; Sernia, Conrad; Bertelli, Eugenio

doi:10.1677/joe.0.1790081

Cited by 17 publications

(7 citation statements)

References 57 publications

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“…In detail, we proved the following constituents of RAS to be present in the BRIN-BD11 rat insulinoma cell line: ACE, AT1bR, AT2R, ACE2, NEP, Mas, APA, APN and IRAP, but not AT1aR. These results are in agreement with those of previous studies, demonstrating the expression of (pro)renin ( 48 , 49 ) , angiotensinogen ( 50 – 52 ) , ACE ( 49 – 53 ) and ACE2 ( 49 ) , AT1R ( 48 , 50 , 53 ) and AT2R ( 53 , 54 ) , Mas ( 55 ) and IRAP ( 56 , 57 ) in several islet-specific cell types, specifically in β-cells, in various species including humans, rats, mice and canines ( 28 ) . In this study, to our knowledge, we demonstrate for the first time the expression of APA, APN and NEP in the BRIN-BD11 pancreatic β-cell line, thus proving the presence of local RAS on β-cells.…”

Section: Discussionsupporting

confidence: 92%

High glucose activates the alternative ACE2/Ang-(1-7)/Mas and APN/Ang IV/IRAP RAS axes in pancreatic β-cells

Härdtner

Mörke

Walther

et al. 2013

International Journal of Molecular Medicine

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The activation of the classical angiotensin (Ang)-converting enzyme (ACE)/Ang II/Ang II type 1 receptor (AT1R) axis of the renin-angiotensin system (RAS) has been associated with islet dysfunction and insulin resistance. Hyperglycaemia, hypertension and obesity, major components of metabolic syndrome, are all associated with increased systemic and tissue levels of Ang II. Whereas it is well established that Ang II, by binding to AT1R, impairs glucose-stimulated insulin secretion and insulin signaling, the contribution of alternative RAS axes to β-cell function remains to be fully elucidated. In this study, using the BRIN-BD11 rat insulinoma cell line, we i) examined the basal expression levels of components of classical and alternative RAS axes and ii) investigated the effects of normal (5.5 mM) and elevated (11, 15, 25 mM) glucose concentrations on their expression and/or enzymatic activity by means of reverse transcription quantitative PCR (RT-qPCR), immunoblot analysis and enzymatic activity assays. The results correlated with the insulin production and release. Essential components of all RAS axes were found to be expressed in the BRIN-BD11 cells. Components of the alternative RAS axes, ACE2, neutral endopeptidase 24.11, Mas receptor (Mas), aminopeptidases A (APA) and N (APN) and insulin-regulated aminopeptidase (IRAP) showed an increased expression/activity in response to high glucose. These alterations were paralleled by the glucose-dependent increase in insulin production and release. By contrast, components of the classical RAS axis, ACE, AT1R and Ang II type 2 receptor (AT2R), remained largely unaffected under these conditions. Glucose induced the activation of the alternative ACE2/Ang-( 1 - 7 )/Mas and APN/Ang IV/IRAP RAS axes simultaneously with the stimulation of insulin production/release. Our data suggest the existence of a functional link between the local RAS axis and pancreatic β-cell function; however, further studies are required to confirm this hypothesis.

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Section: Discussionsupporting

confidence: 92%

High glucose activates the alternative ACE2/Ang-(1-7)/Mas and APN/Ang IV/IRAP RAS axes in pancreatic β-cells

Härdtner

Mörke

Walther

et al. 2013

International Journal of Molecular Medicine

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“…Angiotensinogen (Agt) mRNA has been detected in rat pancreas (Lau et al 2004). Agt is detectable in glucagon-secreting cells (Regoli et al 2003) and in a subset of PP-producing cells (E. Bertelli, unpublished data). Moreover, an angiotensin II (Ang II)-generating system has been reported in isolated rat islets of Langerhans (Lau et al 2004).…”

Section: Other Islet Metabolites As Candidates To Influencementioning

confidence: 97%

“…This is probably the case for Ang II, because AT receptors have been assigned to the luminal pole of duct cells (Leung et al 1997). Agt secretion in the pancreatic juice has been systematically observed in rat pancreas (Regoli et al 2003), and Ang II can be generated via unconventional pathways not involving renin and ACE. Other enzymes are capable of cleaving Agt and release Ang II.…”

Section: Exocrine Secretion Of Hormonesmentioning

confidence: 99%

Association between Endocrine Pancreas and Ductal System. More than an Epiphenomenon of Endocrine Differentiation and Development?

Bertelli

Bendayan

2005

J Histochem Cytochem.

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S U M M A R YTraditional histological descriptions of the pancreas distinguish between the exocrine and the endocrine pancreas, as if they were two functionally distinct glands. This view has been proven incorrect and can be considered obsolete. Interactions between acinar and islet tissues have been well established through numerous studies that reveal the existence of anatomical and functional relationships between these compartments of the gland. Less attention, however, has traditionally been paid to the relationships occurring between the endocrine pancreas and the ductal system. Associations between islet tissue and ducts are considered by most researchers as only a transient epiphenomenon of endocrine development. This article reviews the evidence that has emerged in the last 10 years demonstrating the existence of stable, close, and systematic relationships between these two pancreatic compartments. Functional and pathophysiological implications are considered, and the existence of an "acinar-duct-islet" axis is put forward. The pancreas appears at present to be an integrated organ composed of three functionally related components of well-orchestrated endocrine and exocrine physiological responses.

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“…RAS components were recently identified in human and rodent pancreatic islet cells [28,29]. The precursor angiotensinogen was found in the -cells of the islet [30], whereas, renin and ACE, the best evidence for a complete RAS, were detected in different area of the islet. ACE was found mainly at the periphery of the islet and microvasculature [31].…”

Section: Endocrine Pancreas and Its Local Rasmentioning

confidence: 99%

Angiotensin II in Type 2 Diabetes Mellitus

Chu¹,

Leung

2009

CPPS

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Angiotensin II (Ang II) is well-known as a systemic vasoconstrictor but recently a novel role for the peptide in endocrine function has been suggested and it has been linked to the pathophysiology of type 2 diabetes mellitus. According to several large-scale clinical studies, blocking Ang II prevented the onset of type 2 diabetes in potential patients. Type 2 diabetes is a complicated disease that is primarily characterized by insulin resistance and relative insulin deficiency mediated by numerous organs. Among these organs, the pancreas, adipose tissue, skeletal muscle and liver are the most prominent in maintaining glucose homeostasis. Interestingly, locally generated Ang II has been identified in these organs, where it plays different physiological roles and is produced in relatively high amounts with significant function. In type 2 diabetic human patients or animal models, Ang II, its generating enzymes and receptors are up-regulated and trigger detrimental effects. Moreover, Ang II seems to play roles in the regulation of insulin secretion by the pancreatic beta-cell and insulin sensitivity by peripheral tissues, which are two critical factors contributing to the development of type 2 diabetes. Accordingly, inhibiting Ang II produced beneficial effects on individual organs and throughout the body. Therefore, the present review discusses the role of Ang II in particular organs during normal physiological conditions as well as in type 2 diabetes.

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Angiotensinogen localization and secretion in the rat pancreas

Cited by 17 publications

References 57 publications

High glucose activates the alternative ACE2/Ang-(1-7)/Mas and APN/Ang IV/IRAP RAS axes in pancreatic β-cells

High glucose activates the alternative ACE2/Ang-(1-7)/Mas and APN/Ang IV/IRAP RAS axes in pancreatic β-cells

Association between Endocrine Pancreas and Ductal System. More than an Epiphenomenon of Endocrine Differentiation and Development?

Angiotensin II in Type 2 Diabetes Mellitus

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