Increased susceptibility of <i>db/db</i> mice to rosiglitazone-induced plasma volume expansion: role of dysregulation of renal water transporters

Zhou, Li; Liu, Gang; Jia, Zhanjun; Yang, Kefan; Sun, Ying; Kakizoe, Yutaka; Liu, Mi; Zhou, Shu‐Feng; Ren, Chao; Yang, Baoxue; Yang, Tianxin

doi:10.1152/ajprenal.00004.2013

Cited by 19 publications

(15 citation statements)

References 26 publications

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“…First, this effect might be related to the glycemic control by Rosi. As shown by previous reports, Rosi markedly decreased the blood glucose level in db/db mice [23, 33–35]. Our result also showed that a moderate hyperglycemia in this obese-diabetic db/db mouse strain was almost normalized following 1-week Rosi therapy.…”

Section: Discussionsupporting

confidence: 90%

PPARγAgonist Rosiglitazone Suppresses Renal mPGES-1/PGE2 Pathway in db/db Mice

et al. 2013

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Evidence had shown the detrimental effect of prostaglandin (PG) E2 in diabetic nephropathy (DN) of STZ-induced type-1 diabetes but its role in the development of DN of type-2 diabetes remains uncertain. The present study was undertaken to investigate the regulation of PGE2 synthetic pathway and the interaction between peroxisome proliferator-activated receptor (PPAR)γ and PGE2 synthesis in the kidneys of db/db mice. Strikingly, urinary PGE2 was remarkably elevated in db/db mice paralleled with the increased protein expressions of COX-2 and mPGES-1. In contrast, the protein expressions of COX-1, mPGES-2, cPGES, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) were not altered. Following 1-week rosiglitazone (Rosi) therapy, urinary PGE2, but not other prostanoids, was reduced by 57% in parallel with significant reduction of mPGES-1 protein and EP4 mRNA expressions. By immunohistochemistry, mPGES-1 was significantly induced in the glomeruli of db/db mice, which was almost entirely abolished by Rosi. In line with the reduction of glomerular mPGES-1, the glomerular injury score showed a tendency of improvement after 1 week of Rosi therapy. Collectively, the present study demonstrated an inhibitory effect of PPARγ activation on renal mPGES-1/PGE2/EP4 pathway in type-2 diabetes and suggested that mPGES-1 may potentially serve as a therapeutic target for treating type-2 diabetes-associated DN.

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Section: Discussionsupporting

confidence: 90%

PPARγAgonist Rosiglitazone Suppresses Renal mPGES-1/PGE2 Pathway in db/db Mice

et al. 2013

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“…Skeletal muscle myosin enzymatic activity is required for pulmonary myofibroblast contractility (Walker et al ., ; Rice and Leinwand, ), and increased intracellular calcium has a notable effect on the activity of the adult fast myosin heavy chain promoters (Allen and Leinwand, ). Additionally, low serum potassium promotes the development of diabetes and increases the risk of lethal ventricular arrhythmias in patients with ischaemic heart disease, heart failure and left ventricular hypertrophy (He and MacGregor, ), and increased urinary Na + excretion and urine volume are exhibited in natriuresis (Zhou et al ., ). Herein, we feel that further study is necessary to assess the effects of GNP exposure on the physiological condition (Park et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Pulmonary persistence of graphene nanoplatelets may disturb physiological and immunological homeostasis

Park

Lee

et al. 2016

J. Appl. Toxicol.

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Accumulated evidence suggests that chronic pulmonary accumulation of harmful particles cause adverse pulmonary and systemic health effects. In our previous study, most of the graphene nanoplatelet (GNP) remained in the lung until 28 days after a single instillation. In this study, we sought to evaluate the local and systemic health effect after a long pulmonary persistence of GNP. As expected, GNP remained in the lung on day 90 after a single intratracheal instillation (1.25, 2.5 and 5 mg kg ). In the lung exposed at the highest dose, the total number of cells and the percentage of lymphocytes significantly increased in the BAL fluid with an increase in both the number of GNP-engulfed macrophages and the percentage of apoptotic cells. A Th1-shifted immune response, the elevated chemokine secretion and the enhanced expression of cytoskeletal-related genes were observed. Additionally, the expression of natriuretic-related genes was noteworthy altered in the lungs. Moreover, the number of white blood cells (WBC) and the percentage of macrophages and neutrophils clearly increased in the blood of mice exposed to a 5-mg kg dose, whereas total protein, BUN and potassium levels significantly decreased. In conclusion, we suggest that the long persistence of GNP in the lung may cause adverse health effects by disturbing immunological- and physiological-homeostasis of our body. Copyright © 2016 John Wiley & Sons, Ltd.

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“…This includes weight gain, fluid retention, bone mineral density reduction, and excess myocardial infarction [24]. The fluid retention induced by TZDs has also been proven to significantly increase urine volume and excretion of sodium [25]. Because of this, there is some controversy surrounding the safety of longterm TZD usage to treat diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…This may signify a stage shift, by pioglitazone treatment, from developing cancer. PPARγ agonism has also been shown to increase the antitumor effects of histone deacetylase inhibitors in multiple myeloma cells [25].…”

Section: Discussionmentioning

confidence: 99%

Pioglitazone Alters the Proteomes of Normal Bladder Epithelial Cells but Shows No Tumorigenic Effects

et al. 2020

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Purpose: Pioglitazone, an antihyperglycemic drug, is widely used in diabetes mellitus patients with insulin resistance. Although pioglitazone is known to have a potential link to bladder cancer (BC), there have been contradictory results. This present study is designed to understand the regulatory mechanisms that drive the effects of pioglitazone on the bladder epithelial cells.Methods: Labeled liquid chromatography-tandem mass spectrometry-based proteomics profiling characterized the global proteomes of normal human bladder epithelial cells treated with or without pioglitazone.Results: This approach detected approximately 5,769 proteins in total. Of those 5,769 proteins, 124 were identified as being differentially expressed due to pioglitazone treatment. Further analysis identified 95 upregulated and 29 downregulated proteins (absolute log<sub>2</sub> fold change >0.58 and P-value<0.05). The following functional gene enrichment analysis suggested that pioglitazone may be altering a few select biological processes, such as gene/chromatin silencing, by downregulating BMI1 (B lymphoma Mo-MLV insertion region 1 homolog), a polycomb complex protein. Further cell-based assays showed that cell adhesion molecules, epithelial-mesenchymal transition markers, and major signaling pathways were significantly downregulated by pioglitazone treatment.Conclusions: These experimental results revealed the proteomic and biological alterations that occur in normal bladder cells in response to pioglitazone. These findings provided a landscape how bladder proteome is influenced by pioglitazone, which suggests the potential adverse effects of diabetes drugs and their links to bladder dysfunctions.

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Increased susceptibility of db/db mice to rosiglitazone-induced plasma volume expansion: role of dysregulation of renal water transporters

Cited by 19 publications

References 26 publications

PPARγAgonist Rosiglitazone Suppresses Renal mPGES-1/PGE2 Pathway in db/db Mice

PPARγAgonist Rosiglitazone Suppresses Renal mPGES-1/PGE2 Pathway in db/db Mice

Pulmonary persistence of graphene nanoplatelets may disturb physiological and immunological homeostasis

Pioglitazone Alters the Proteomes of Normal Bladder Epithelial Cells but Shows No Tumorigenic Effects

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