Current Research of the RAS in Pancreatitis and Pancreatic Cancer

Leung, Po Sing

doi:10.1007/978-90-481-9060-7_10

Cited by 3 publications

(2 citation statements)

References 86 publications

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“…The mechanistic effect of AGTR1 activation on pancreatic b-cell death is the induction of NADPH oxidase and ROS generation (Shao et al 2006, Leung 2010 (Oliveira et al 2003). The results of this study also indicated that high-glucose medium increased expression of p47 phox mRNA and its protein in both a pancreatic b-cell line and isolated male mouse islets and also increased ROS production in the b-cell line.…”

Section: Discussionsupporting

confidence: 56%

Testosterone reduces AGTR1 expression to prevent β-cell and islet apoptosis from glucotoxicity

Kooptiwut¹,

Hanchang²,

Semprasert³

et al. 2014

Journal of Endocrinology

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Hypogonadism in men is associated with an increased incidence of type 2 diabetes. Supplementation with testosterone has been shown to protect pancreatic b-cell against apoptosis due to toxic substances including streptozotocin and high glucose. One of the pathological mechanisms of glucose-induced pancreatic b-cell apoptosis is the induction of the local rennin-angiotensin-aldosterone system (RAAS). The role of testosterone in regulation of the pancreatic RAAS is still unknown. This study aims to investigate the protective action of testosterone against glucotoxicity-induced pancreatic b-cell apoptosis via alteration of the pancreatic RAAS pathway. Rat insulinoma cell line (INS-1) cells or isolated male mouse islets were cultured in basal and high-glucose media in the presence or absence of testosterone, losartan, and angiotensin II (Ang II), then cell apoptosis, cleaved caspase 3 expression, oxidative stress, and expression of angiotensin II type 1 receptor (AGTR1) and p47 phox mRNA and protein were measured. Testosterone and losartan showed similar effects in reducing pancreatic b-cell apoptosis. Testosterone significantly reduced expression of AGTR1 protein in INS-1 cells cultured in high-glucose medium or high-glucose medium with Ang II. Testosterone decreased the expression of AGTR1 and p47 phox mRNA and protein in comparison with levels in cells cultured in high-glucose medium alone. Furthermore, testosterone attenuated superoxide production when co-cultured with high-glucose medium. In contrast, when cultured in basal glucose, supplementation of testosterone did not have any effect on cell apoptosis, oxidative stress, and expression of AGT1R and p47 phox .In addition, high-glucose medium did not increase cleaved caspase 3 in AGTR1 knockdown experiments. Thus, our results indicated that testosterone prevents pancreatic b-cell apoptosis due to glucotoxicity through reduction of the expression of ATGR1 and its signaling pathway.

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Section: Discussionsupporting

confidence: 56%

Testosterone reduces AGTR1 expression to prevent β-cell and islet apoptosis from glucotoxicity

Kooptiwut¹,

Hanchang²,

Semprasert³

et al. 2014

Journal of Endocrinology

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“…A local function-independent RAS in the pancreas without association in blood circulating hormones bioavailability was previously proposed in the dogs, rodents and human [ 15 16 ]. Pancreatic RAS plays different roles in the pancreatic physiology and pathophysiology regulation as recently reviewed [ 17 ]. For example, the pancreatic RAS may play a critical role for the regulation of pancreatic microcirculation and ductal secretion [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Local Pancreatic Renin-Angiotensin System on the Microcirculation of Rat with Severe Acute Pancreatitis

Pan

Feng

Long

et al. 2015

Korean J Physiol Pharmacol

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Severe acute pancreatitis (SAP) is normally related to multiorgan dysfunction and local complications. Studies have found that local pancreatic renin-angiotensin system (RAS) was significantly upregulated in drug-induced SAP. The present study aimed to investigate the effects of angiotensin II receptors inhibitor valsartan on dual role of RAS in SAP in a rat model and to elucidate the underlying mechanisms. 3.8% sodium taurocholate (1 ml/kg) was injected to the pancreatic capsule in order for pancreatitis induction. Rats in the sham group were injected with normal saline in identical locations. We also investigated the regulation of experimentally induced SAP on local RAS expression in the pancreas through determination of the activities of serum amylase, lipase and myeloperoxidase, histological and biochemical analysis, radioimmunoassay, fluorescence quantitative PCR and Western blot analysis. The results indicated that valsartan could effectively suppress the local RAS to protect against experimental acute pancreatitis through inhibition of microcirculation disturbances and inflammation. The results suggest that pancreatic RAS plays a critical role in the regulation of pancreatic functions and demonstrates application potential as AT1 receptor antagonists. Moreover, other RAS inhibitors could be a new therapeutic target in acute pancreatitis.

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Low-level expression oflet-7ain gastric cancer and its involvement in tumorigenesis by targetingRAB40C

Yang

Jie

Cao

et al. 2011

CARCIN

101

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Current Research of the RAS in Pancreatitis and Pancreatic Cancer

Cited by 3 publications

References 86 publications

Testosterone reduces AGTR1 expression to prevent β-cell and islet apoptosis from glucotoxicity

Testosterone reduces AGTR1 expression to prevent β-cell and islet apoptosis from glucotoxicity

Effects of Local Pancreatic Renin-Angiotensin System on the Microcirculation of Rat with Severe Acute Pancreatitis

Low-level expression oflet-7ain gastric cancer and its involvement in tumorigenesis by targetingRAB40C

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