Similar Aquaporin9 and MAPK Expression Profiles in the Liver of Types 1 and 2 Diabetes Mellitus

Hou, Jiaojiao; Li, Yuan; Ren, Xüxia; Gao, Fei; Chen, Yuqin; Yi, Yaoxing; Kang, Lili; Luo, Yürui; Yang, Mei

doi:10.1055/s-0043-123470

Cited by 8 publications

(3 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High expression of MAFB in human pancreatic beta-cells was reported to increase cellular vulnerability to viral infections associated with the etiology of T1DM 23. Expression of AQP9 was upregulated in the liver in T1DM 24,2526.…”

Section: Discussionmentioning

confidence: 99%

<p>Identification of dynamic molecular networks in peripheral blood mononuclear cells in type 1 diabetes mellitus</p>

Pan

Yang

2019

DMSO

View full text Add to dashboard Cite

Background Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by the immune destruction of islet β cells. Gene expression in peripheral blood mononuclear cells (PBMCs) could offer new disease and treatment markers in T1DM. The objective of this study was to explore the coexpression and dynamic molecular networks in PBMCs of T1DM patients. Methods Dataset GSE9006 contains PBMC samples of healthy volunteers, newly diagnosed T1DM patients, T1DM patients after insulin treatment, and newly diagnosed type 2 diabetes mellitus (T2DM) patients. Weighted correlation network analysis (WGCNA) was used to generate coexpression networks in T1DM and T2DM. Functional pathways in highly correlated modules of T1DM were enriched by gene set enrichment analysis (GSEA). We next filtered the differentially expressed genes (DEGs) and revealed their dynamic expression profiles in T1DM with or without insulin treatment. Furthermore, dynamic clusters and dynamic protein–protein interaction networks were identified. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was developed in dynamic clusters. Results WGCNA disclosed 12 distinct gene modules, and distinguished between correlated networks in T1DM and T2DM. Two modules were closely associated with T1DM. GSEA showed that the immune response and response to cytokines were enriched in the T1DM highly correlated module. Next, we screened 44 DEGs in newly diagnosed T1DM compared with healthy donors, and 71 DEGs in 1-month and 97 DEGs in 4-month insulin treatment groups compared with newly diagnosed T1DM. Dynamic expression profiles of DEGs indicated the potential targets for T1DM treatment. Moreover, four molecular dynamic clusters were analyzed in newly diagnosed and insulin-treated T1DM. Functional annotation showed that these clusters were mainly enriched in the IL-17 signaling pathway, nuclear factor-ϰB signaling pathway, and tumor necrosis factor signaling pathway. Conclusion The results indicate potential drug targets or clinical efficacy markers, as well as demonstrating the underlying molecular mechanisms of T1DM treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

<p>Identification of dynamic molecular networks in peripheral blood mononuclear cells in type 1 diabetes mellitus</p>

Pan

Yang

2019

DMSO

View full text Add to dashboard Cite

show abstract

“…It is important to note that the effects of 10H2DA on PEPCK and G6Pase gene expression in glycometabolism differed from those of insulin. Hou et al () recently reported that AQP9 expression was significantly up‐regulated in type 1 and type 2 diabetes mellitus and suggested that insulin down‐regulated AQP9 by inhibiting phosphorylated JNK and activating phosphorylated p38. Further studies on the signal transduction pathway triggered by 10H2DA will contribute to our understanding of the effects of this acid in metabolism.…”

Section: Discussionmentioning

confidence: 99%

Down‐regulation of aquaporin 9 gene transcription by 10‐hydroxy‐2‐decenoic acid: A major fatty acid in royal jelly

Usui

Soda

Iguchi

et al. 2019

Food Science & Nutrition

View full text Add to dashboard Cite

Abstract10‐Hydroxy‐trans‐2‐decenoic acid (10H2DA) is a unique lipid component of royal jelly produced by worker honeybees that exerts insulin‐like effects. We herein investigated the effects of 10H2DA on the gene expression of aquaporin 9 (AQP9), which functions as a glycerol transporter in the liver, to clarify whether 10H2DA modulates energy metabolism. 10H2DA suppressed AQP9 gene expression in HepG2 cells by promoting the phosphorylation of Akt and AMP‐activated protein kinase (AMPK). This suppression was partially recovered by the treatment of cells with inhibitors for Akt and AMPK. Based on the result showing that leptomycin B partially recovered the suppression of AQP9 gene expression, 10H2DA inhibited the expression of Foxa2, a transcription factor for the AQP9 gene, and also induced its nuclear exclusion. Although 10H2DA up‐regulated phosphoenolpyruvate carboxykinase and glucose‐6‐phosphatase gene expression, this was suppressed through the modulation of Foxa2 by insulin. These results suggest that 10H2DA suppresses AQP9 gene expression through the phosphorylation of Akt and AMPK and down‐regulation of Foxa2 expression.

show abstract

“…The insulin treatment lowered AQP9, probably through the inhibition of p -JNK and activation of phospho-p38. In conclusion, AQP9 and MAPK pathways analysis makes plausible a possible AQP9 regulation through MAPK signaling pathways [ 132 ].…”

Section: Possible Role Of Aqps “Metabolic Network” In Obesity-induced Systemic Insulin Resistancementioning

confidence: 99%

Aquaporins in insulin resistance and diabetes: More than channels!

et al. 2021

View full text Add to dashboard Cite

Aquaporins (AQPs) are part of the family of the integral membrane proteins. Their function is dedicated to the transport of water, glycerol, ammonia, urea, H 2 O 2 , and other small molecules across the biological membranes. Although for many years they were scarcely considered, AQPs have a relevant role in the development of many diseases. Recent discoveries suggest, that AQPs may play an important role in the process of fat accumulation and regulation of oxidative stress, two crucial aspects of insulin resistance and type-2 diabetes (T2D). Insulin resistance (IR) and T2D are multi-faceted systemic diseases with multiple connections to obesity and other comorbidities such as hypertension, dyslipidemia and metabolic syndrome. Both IR and T2D transcends different tissues and organs, creating the maze of mutual relationships between adipose fat depots, skeletal muscle, liver and other insulin-sensitive organs. AQPs with their heterogenous properties, distinctive tissue distribution and documented involvement in both the lipid metabolism and regulation of the oxidative stress appear to be feasible candidates in the search for the explanation to this third-millennium plague. A lot of research has been assigned to adipose tissue AQP7 and liver tissue AQP9, clarifying their relationship and coordinated work in the induction of hepatic insulin resistance. Novel research points also to other aquaporins, such as AQP11 which may be associated with the induction of insulin resistance and T2D through its involvement in hydrogen peroxide transport. In this review we collected recent discoveries in the field of AQP's involvement in the insulin resistance and T2D. Novel paths which connect AQPs with metabolic disorders can give new fuel to the research on obesity, insulin resistance and T2D - one of the most worrying problems of the modern society.

show abstract

Similar Aquaporin9 and MAPK Expression Profiles in the Liver of Types 1 and 2 Diabetes Mellitus

Cited by 8 publications

References 33 publications

<p>Identification of dynamic molecular networks in peripheral blood mononuclear cells in type 1 diabetes mellitus</p>

<p>Identification of dynamic molecular networks in peripheral blood mononuclear cells in type 1 diabetes mellitus</p>

Down‐regulation of aquaporin 9 gene transcription by 10‐hydroxy‐2‐decenoic acid: A major fatty acid in royal jelly

Aquaporins in insulin resistance and diabetes: More than channels!

Contact Info

Product

Resources

About