Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to characterize the eventual presence and molecular forms of gelatinase/type IV collagenase activities in gingival crevicular fluid (GCF) and saliva in different forms of periodontitis; patients with clinically healthy periodontium served as controls. Enzyme activities were monitored electrophoretically by zymography using gelatin and type IV collagen as substrates and analyzed visually and/or densitometrically. Both saliva and GCF collected from adult periodontitis, localized juvenile periodontitis and type II diabetes mellitus periodontitis patients contained species moving identically with gelatinase isolated from human neutrophils or MMP-9 (mean 98 kD), and species with mobility similar to gelatinase in fibroblast cell culture supernatants or MMP-2 (mean 76 kD). Hitherto, undescribed high molecular weight forms (mean 128 kD), were found, possibly representing polymerized or complexed enzyme active/activated in situ in the gel matrix. Small molecular forms of gelatinases (mean 51 kD and 46 kD), unable to cleave type IV collagen, were also found, most likely representing in vivo proteolytically activated, truncated enzymes. Although multiple forms of gelatinases/type IV collagenases in saliva and GCF may take part in the tissue destruction in periodontitis, their profile judged according to molecular weights does not differentiate between different forms of periodontitis.
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PMID:Multiple forms of gelatinases/type IV collagenases in saliva and gingival crevicular fluid of periodontitis patients. 812 40

The pathologic hallmarks of diabetic nephropathy are excess mesangial extracellular matrix (ECM) and mesangial cell proliferation. We previously showed that mesangial cell phenotypic changes play an important role in the pathogenesis of diabetic nephropathy. We concluded that phenotypic changes were present in bone marrow (BM)-derived mesangial cell progenitors, as transplantation of BM from db/db mice, a model of type 2 diabetic nephropathy, transferred the db genotype and a nephropathy phenotype to naive B6 mice recipients. The recipients did not develop diabetes; however, they did develop albuminuria and glomerular lesions mirroring those in the donors (i.e., glomerular hypertrophy, increased ECM, and increased cell number with cell proliferation). We found that matrix metalloproteinase 2 (MMP-2) facilitated invasion of the mesangial cells into ECM and proliferation in vitro. Thus, increased MMP-2 activity in db/db mesangial cell progenitors may partially explain increased mesangial cell repopulation and proliferation in B6 recipients of db/db BM. In summary, BM-derived mesangial cell progenitors may play a crucial role in the development and progression of ECM accumulation and mesangial cell proliferation in this model of diabetic nephropathy in type 2 diabetes.
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PMID:Development of albuminuria and glomerular lesions in normoglycemic B6 recipients of db/db mice bone marrow: the role of mesangial cell progenitors. 1533 54

Type 2 diabetes mellitus (T2DM) has been considered to be a risk factor for numerous human cancers. Hyperglycemia is one of the most direct internal environmental changes for patients with T2DM. Increasing evidence reveals that a high concentration of glucose can promote tumor progression, while its role for migration and invasion of invasive ductal breast carcinoma (IDBC) cells remains unclear. In the present study, it was demonstrated that IDBC patients with T2DM suffered an increased tumor size and more frequent lymphatic and distant metastasis compared with those without T2DM (P<0.05). MCF-7 breast carcinoma cells, which were cultured in a high glucose concentration medium (25.00 mM), exhibited increased invasion (P<0.05). In addition, the expression of glucose transporters (Gluts), matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in IDBC tissues with T2DM was significantly higher compared to those without T2DM. Downregulation of glucose transporter 1 (Glut1) by small interfering RNA may markedly suppress MCF-7 cell invasion as well as the expression of MMP2 and MMP9. These results suggest that T2DM can affect the malignant features of tumors in IDBC. The high glucose concentration in the tumor microenvironment may enhance IDBC invasion via upregulating Glut1/MMP2/MMP9 axis expression.
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PMID:High-concentration glucose enhances invasion in invasive ductal breast carcinoma by promoting Glut1/MMP2/MMP9 axis expression. 2852 6

Dipeptidyl peptidase-IV (DPP-IV) inhibitors are used to control blood glucose levels in patients with type 2 diabetes. However, the influence of DPP-IV inhibitors on malignant tumors remains unknown. The present study aimed to investigate the effect of the DPP-IV inhibitor saxagliptin on thyroid carcinoma cells. Transwell assays and a nude mouse lung metastasis model were used to evaluate the invasion and metastasis of thyroid carcinoma cells. Western blotting was used to determine the protein levels of migration and invasion-related molecules. We tested the expression and distribution of nuclear factor, erythroid 2 like 2 (NRF2) in thyroid carcinoma cells with and without saxagliptin. Furthermore, we silenced NRF2 and observed saxagliptin's effect on migration and invasion. Quantitative real-time reverse transcription PCR (qRT-PCR) and western blotting were then used to measure the expression of NFR2's downstream molecules (heme oxygenase 1 (HO1), matrix metalloproteinase 2 (MMP2), and vascular endothelial growth factor (VEGF)). A luciferase reporter assay was used to validate whether NRF2 could regulate the transcriptional activity of the HO1 promoter. Saxagliptin enhanced the migratory and invasive ability of thyroid carcinoma cells. MMP2 and VEGF levels were also elevated by saxagliptin treatment. We found that saxagliptin treatment increases the nuclear and cytoplasmic accumulation NRF2. Silencing NRF2 abolished the effect of saxagliptin on migration and invasion. Accordingly, NRF2 silencing downregulated HO1, MMP2, and VEGF levels. The luciferase assay showed that NRF2 activated transcription from the HO1 promoter. Saxagliptin could promote this transcriptional activity by upregulating NRF2. Saxagliptin enhanced the migratory and invasive ability of human thyroid carcinoma cells, as well as the expression of MMP2 and VEGF, by activating the NRF2/HO1 pathway.
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PMID:The DPP-IV inhibitor saxagliptin promotes the migration and invasion of papillary thyroid carcinoma cells via the NRF2/HO1 pathway. 3300 Dec 78