The renin&amp;ndash;angiotensin system and diabetes: An update

Simoes-e-Silva, Ana

doi:10.2147/vhrm.s1905

Cited by 153 publications

(27 citation statements)

References 171 publications

(224 reference statements)

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“…The Ang II receptor, AT1, is primarily known to mediate vasoconstriction, oxidative stress, and inflammation, 35 while AT2 overall exerts beneficial properties such as vasodilation, anti-inflammatory, and anti-fibrotic effects. 36 In human islets, inhibition of AT1 receptor reduced ER stress and improved its antioxidant potential and insulin secretion.…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum (ER) Stress in Part Mediates Effects of Angiotensin II in Pancreatic Beta Cells

Ramalingam¹,

Sopontammarak²,

Menikdiwela³

et al. 2020

DMSO

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Introduction: The renin angiotensin aldosterone system (RAAS) is a hormone system known for its role in regulating blood pressure and fluid balance. Numerous RAAS inhibitors routinely prescribed for hypertension have also beneficial effects in type 2 diabetes (T2D) prevention. RAAS components are expressed locally in many tissues, including adipose tissue and pancreas, where they exert metabolic effects through RAAS bioactive hormone angiotensin II (Ang II). Pancreatic beta cells are specialized insulin-producing cells; they have also developed endoplasmic reticulum (ER), which contributes to beta cell dysfunction, when proteins are misfolded in disease states such as T2D. However, no studies have investigated the relationship between RAAS and ER stress in beta cells as a mechanism linking pancreatic RAAS to T2D. Hence, we hypothesized that Ang II treatment of beta cells increases ER stress and inflammation leading to reduced insulin secretion. Methods: To test this hypothesis, we treated clonal INS-1E beta cells and human islets with Ang II and assessed changes in ER stress markers. INS-1E beta cells were also used for measuring insulin secretion and for assessing the effects of various RAAS and ER stress inhibitors. Results: We demonstrated that Ang II significantly increased the expression of ER stress genes such as Chop and Atf4 and reduced insulin secretion. Furthermore, inhibition of Ang II production with an angiotensin converting enzyme inhibitor (ACEi, captopril) significantly reduced ER stress. Moreover, the Ang II receptor blockade reduced ER stress significantly and rescued insulin secretion. Discussion: This research provides new mechanistic insight into the role of RAAS activation via ER stress on beta cell dysfunction and provides additional evidence for protective effects of RAAS inhibition in T2D.

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Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum (ER) Stress in Part Mediates Effects of Angiotensin II in Pancreatic Beta Cells

Ramalingam¹,

Sopontammarak²,

Menikdiwela³

et al. 2020

DMSO

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“…Meaning that underlying inflammation, either caused in the lung, or coming from another site (e.g., cardiovascular diseases, obesity, diabetes, and liver disease) may feedback into the lung upon a new infection like SARS-CoV2, resulting in the exacerbation of the local and systemic inflammation. The RAS-KKS system is also already affected in all those risk groups conditions, including aging (56)(57)(58)(59)(60)(61)(62)(63)(64).…”

Section: Box 2 | Risk Groupsmentioning

confidence: 99%

Overview: Systemic Inflammatory Response Derived From Lung Injury Caused by SARS-CoV-2 Infection Explains Severe Outcomes in COVID-19

Polidoro

Hagan

Santiago³

et al. 2020

Front. Immunol.

163

147

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Most SARS-CoV2 infections will not develop into severe COVID-19. However, in some patients, lung infection leads to the activation of alveolar macrophages and lung epithelial cells that will release proinflammatory cytokines. IL-6, TNF, and IL-1β increase expression of cell adhesion molecules (CAMs) and VEGF, thereby increasing permeability of the lung endothelium and reducing barrier protection, allowing viral dissemination and infiltration of neutrophils and inflammatory monocytes. In the blood, these cytokines will stimulate the bone marrow to produce and release immature granulocytes, that return to the lung and further increase inflammation, leading to acute respiratory distress syndrome (ARDS). This lung-systemic loop leads to cytokine storm syndrome (CSS). Concurrently, the acute phase response increases the production of platelets, fibrinogen and other pro-thrombotic factors. Systemic decrease in ACE2 function impacts the Renin-Angiotensin-Kallikrein-Kinin systems (RAS-KKS) increasing clotting. The combination of acute lung injury with RAS-KKS unbalance is herein called COVID-19 Associated Lung Injury (CALI). This conservative two-hit model of systemic inflammation due to the lung injury allows new intervention windows and is more consistent with the current knowledge.

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“…9 In diabetic rats, the angiotensin II level in the kidney is elevated compared to normal rats, 7,18,19 however the level of renin granulation in the afferent arterioles is also higher than normal. 8 In diabetic rats, angiotensin II AT1-A and AT1-B receptors are downregulated on both the renin-positive and renin-negative SMCs surfaces ( Figure 3A and B). 9 The difference in the number of AT1-A receptors between the renin-positive and renin-negative SMCs is same as in normal rats, the downregulation of AT1-B are enhanced in the reninpositive than in renin-negative SMCs ( Figure 3A and B).…”

Section: Distribution Of Angiotensin II At1 Receptors On Kidney Artermentioning

confidence: 92%

“…4,6 In diabetes, the balance of trans-differentiation between renin-positive and renin-negative SMCs exhibits elevated renin granulation in afferent arterioles, while the kidney tissue level of angiotensin II is also elevated. 7,8 This discrepancy is a particularity of diabetes, in which the number of angiotensin II AT1 receptor subtypes are estimated using stereological principles in afferent and efferent arterioles as renin-positive SMCs and renin-negative SMCs makes out it. 9 The purpose of this review is to summarize the stereological data of some molecules involved in the JGA.…”

Section: Introductionmentioning

confidence: 99%

Functional Relevancies of Trans-Differentiation in the Juxtaglomerular Apparatus of Rat Kidney

Rázga

2020

IJNRD

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Glomerular filtration rate is controlled by the contractile effect of angiotensin II on afferent and efferent arterioles. The renin positivity of the afferent arterioles depends on tubuloglomerular feedback via the macula densa (MD) and short loop feedback via the afferent arteriolar endothelia. The renin-producing cells are trans-differentiated from smooth muscle cells (SMCs) of mainly the afferent arterioles, the MD cells are trans-differentiated from the neighboring tubular cells, and the high-permeability endothelial cells are transdifferentiated from normal permeability endothelial cells facing the renin-negative part of the afferent arterioles. All of the trans-differentiations depend on the activity of the reninangiotensin system (RAS). The distribution of AT1 receptors for angiotensin II expresses the contractile effects of angiotensin II on renin-negative SMCs and the negative effect on trans-differentiation of renin-positive SMCs and MD cells. The purpose of this review is to summarize the stereological data of molecules like angiotensin II AT1 receptors, L-type calcium channels, and renin receptors in the juxtaglomerular apparatus of normal and STZinduced diabetic rat kidneys, thus showing their functional relevancies on trans-differentiation among the juxtaglomerular apparatus' elements.

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The renin–angiotensin system and diabetes: An update

Cited by 153 publications

References 171 publications

<p>Endoplasmic Reticulum (ER) Stress in Part Mediates Effects of Angiotensin II in Pancreatic Beta Cells</p>

<p>Endoplasmic Reticulum (ER) Stress in Part Mediates Effects of Angiotensin II in Pancreatic Beta Cells</p>

Overview: Systemic Inflammatory Response Derived From Lung Injury Caused by SARS-CoV-2 Infection Explains Severe Outcomes in COVID-19

<p>Functional Relevancies of Trans-Differentiation in the Juxtaglomerular Apparatus of Rat Kidney</p>

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