A High-Fat/High-Sucrose Diet Induces WNT4 Expression in Mouse Pancreatic β-cells

Kurita, Yayoi; Ohki, Tsuyoshi; Soejima, Eri; Yuan, Xiaohong; Kakino, Satomi; Wada, Nobuhiko; Hashinaga, Toshihiko; Nakayama, Hitomi; Tani, Junichi; Tajiri, Yuji; Hiromatsu, Yuji; Yamada, Kentaro; Nomura, Masatoshi

doi:10.2739/kurumemedj.ms652008

Cited by 21 publications

(22 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies showed that insulin secretion of β -cell line MIN6 increased significantly at high glucose concentration, and its insulin secretion and S-type response curve were similar to those of normal islet cells. Further studies on insulin secretion, glucose transport, glycooxidative phosphorylation, and glucose utilization of insulin β -cell line MIN6 showed that the cell components in MIN6 cells that regulate glucose concentration-dependent insulin secretion are similar to normal islets in quality and quantity [ 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

High T3 Induces β-Cell Insulin Resistance via Endoplasmic Reticulum Stress

Liang

Liu

Huang

et al. 2020

Mediators of Inflammation

View full text Add to dashboard Cite

Hyperthyroidism can cause glucose metabolism disorders and insulin resistance. Insulin resistance in muscle and adipose tissues has been extensively studied, whereas investigations on β-cell insulin resistance are limited. This study preliminarily explored the effects of high T3 levels on β-cell line (MIN6) insulin resistance, as well as the roles of endoplasmic reticulum stress (ERS). In this study, we treated β-cell line with T3, with or without an inhibitor of phosphotyrosine phosphatases (PTPs, sodium vanadate) or ERS inhibitor (4-PBA). The results indicated that high levels of T3 significantly inhibited insulin secretion in β-cell line. In addition, we observed an upregulation of p-IRS-1ser307 and downregulation of Akt. These results can be corrected by sodium vanadate. Moreover, high T3 levels upregulate the ERS-related proteins PERK, IRE1, ATF6, and GRP78, as well as ERS-related apoptosis CHOP and caspase-12. Similarly, this change can be corrected by 4-PBA. These results suggest that high T3 levels can induce insulin resistance in β-cell line by activating ERS and the apoptotic pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

High T3 Induces β-Cell Insulin Resistance via Endoplasmic Reticulum Stress

Liang

Liu

Huang

et al. 2020

Mediators of Inflammation

View full text Add to dashboard Cite

show abstract

“…For example, FZD3 was proved to be required for the development of embryonic pancreas in mice [40]. FZD4 may be involved in the regulation of β-cell functions in mouse [41]. More gene and clinical evidence are needed to explore their potential values.…”

Section: Discussionmentioning

confidence: 99%

Expression and Prognostic Impact of FZDs in Pancreatic Adenocarcinoma

Liu

Zhang

2020

Preprint

View full text Add to dashboard Cite

Background: Despite the high number of researches on pancreatic adenocarcinoma (PAAD) over past decades, little progress had been made due to lack of effective treatment regimens. we aimed to investigate the expression level, mutation, and clinical significance of the Frizzled (FZD) family in PAAD so as to establish a sufficient scientific evidence for clinical decisions and risk management.Methods: PAAD samples were extracted from The Cancer Genome Atlas (TCGA). Oncomine, Gene expression profiling interactive analysis (GEPIA), Human Protein Atlas (HPA), Kaplan-Meier Plotter, cBioPortal, LinkedOmics, DAVID database, and R software (x64 3.6.2) were used to comprehensively analyze the roles of FZDs. p-value below to 0.05 was considered as significant difference.Results: In total, 179 PAAD tissues and 171 paracancerous tissues were included. The expression levels of FZD1, 2, 6, 7, and 8 were higher in PAAD tissues than those in normal pancreatic tissue. The higher the expression levels of FZD2 and FZD7, the higher the clinical stage. PAAD patients with high expression of FZD6 had shorter overall survival (OS) than those with low expression, indicating that FZD6 could be a potential prognostic and predictive marker in PAAD. PAAD patients with high expression of FZD8 had shorter recurrence free survival (RFS) than those with low expression, indicating that FZD8 could be a potential therapeutic target in PAAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that FZDs played a critical role in the Wnt signaling pathway, which was further confirmation that FZDs were transmembrane receptors of Wnt signaling pathway. Conclusions: Our results strongly indicated a crucial role of the FZD family in PAAD. FZD3, 4, 5, 6, and 9 could be potential prognostic and predictive markers, and FZD4 and 8 might function as potential therapeutic targets in PAAD.

show abstract

“…57 Similarly, cellular proliferation and GSIS of β-cell line MIN6 are not affected when exposed to Wnt4 protein, but suppressed significantly when knockdown of Wnt4. 58 therefore, restoring Wnt4 or Wnt5a significantly alleviates TGF-β1mediated fibrosis in diabetic kidneys. 62 Similarly, melatonin, simvastatin, Salvia miltiorrhiza extracts and liraglutide treatment block the apoptosis of mesangial cells and improve the renal injury of diabetic rat by restoring the canonical Wnt signalling mediated by Wnt4 and Wnt5a.…”

Section: Wnt4mentioning

confidence: 91%

“…Wnt5b expression is up-regulated in islets of mice fed with high-fat diet (HFD), and UK Caucasian individuals carrying IVS3C>G variant (rs2270031) in the Wnt5b gene are predispose to T2DM. 58,98 Although the exact role of Wnt5b in the regulation of β-cell proliferation and functions has not been elucidated, silencing the noncanonical Wnt pathways induced by Wnt4/Wnt5a/Wnt5b and canonical Wnt3a/β-catenin signalling together could drive the immature hiPSC-derived S7 cells towards a mature phenotype, indicating the potential inhibitory effect of Wnt5b on the maturation of β-cells. 48 Subsequent in vitro experiments showed that compared with the inhibitory effect on adipogenesis via activation of canonical Wnt signalling mediated by Wnt1 and Wnt10b, Wnt5b…”

Section: Wnt5a and Wnt5bmentioning

confidence: 99%