• Journal of Korean Foot and Ankle Society
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• v.20 no.3
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• pp.121-125
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• 2016

Purpose: This study investigates the amputation rate within 1 year after the diagnosis of diabetic foot ulcer and its associated risk factors. Materials and Methods: This study enrolled 60 patients with diabetic foot ulcer. The mean and standard deviation age was $64.4{\pm}12.8years$ (range, 32~89 years); the mean and standard deviation prevalence period for diabetes mellitus was $21.0{\pm}7.5years$ (range, 0.5~36 years). The amputation rate was evaluated by dividing the subjects into two groups - the major and minor amputation groups - within 1 year following the initial diagnosis of diabetic foot ulcer. Multivariate Cox proportional hazards regression analysis was used to identify the risk factors for amputation. Results: The total amputation rate of 38.3% (n=23) was comprised of the amputation rate for the major amputation group (10.0%) and rate for the minor amputation group (23.8%). There was a high correlation between peripheral artery disease (toe brachial pressure index <0.7) and amputation (hazard ratio [HR] 5.81, confidence interval [CI] 2.09~16.1, p<0.01). Nephropathy was significantly correlated with the amputation rate (HR 3.53, CI 1.29~9.64, p=0.01). Conclusion: Clinicians who treat patients with diabetic foot complications must understand the fact that the amputation rate within 1 year is significant, and that the amputation rate of patients with peripheral artery disease or nephropathy is especially high.

• Korean Journal of Pharmacognosy
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• v.45 no.4
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• pp.354-358
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• 2014

Aldose reductase (AR) has been demonstrated to play important role in the development of the diabetic complications such as diabetic retinopathy, diabetic neuropathy and diabetic nephropathy. To discover novel treatments for diabetic complications from natural sources, 69 Korean herbal medicines have been investigated for inhibitory activities on AR. Among them, 7 herbal medicines, Eleutherococcus sessiliflorus (stems), Artemisia japonica (whole plants), Wisteria floribunda (leaves), Eurya japonica (stems, twigs and leaves, leaves), Ampelopsis brevipedunculata (stems) exhibited a significant inhibitory activity compared with 3,3-tetramethyleneglutaric acid as positive control.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.5
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• pp.299-305
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• 2011

Calcineurin (CaN) is activated in diabetes and plays a role in glomerular hypertrophy and extracellular matrix (ECM) accumulation. Here, kidneys from diabetic model mice were investigated for the expression of the regulator of CaN 1 (RCAN1) isoform 4 (RCAN1.4) which had been shown to be transcriptionally upregulated by CaN activation. We found the increased immunoreactivity for RCAN1 in the glomerular cells of db/db mice and streptozotocin-induced diabetic mice. In concordance, the expression of RCAN1 protein and RCAN1.4 mRNA were elevated in the whole kidney sample from db/db mice. Interleukin-$1{\beta}$ (IL-$1{\beta}$), tumor necrosis factor-${\alpha}$, and glycated albumin (AGE-BSA) were identified as inducers of RCAN1.4 in mesangial cells. Pretreatment of cyclosporine A blocked the increases of RCAN1.4 stimulated by IL-$1{\beta}$ or AGE-BSA, suggesting that activation of CaN is required for the RCAN1.4 induction. Stable transfection of RCAN1.4 in Mes-13 mesangial cells upregulated several factors relevant to ECM production and degradation. These results suggested that RCAN1.4 might act as a link between CaN activation and ECM turnover in diabetic nephropathy.

• The Journal of the Korean life insurance medical association
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• v.30 no.2
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• pp.16-19
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• 2011

In patents with diabetes, the higher the serum glucose level was, the more cardiovascular events and death were observed. But with a certain kind of group, to control glucose level tightly does not decrease the incidence of these events. Several studies show that intensive glucose control does not gain benefit in patient with long standing, uncontrolled diabetes, especially having previous cardiovascular events, while definitely preventing progression of newly onset of diabetic nephropathy. Whether intensive glucose control increases mortality in high risk group is obscure and needs more studies with longer observation time.

• BMB Reports
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• v.43 no.3
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• pp.188-192
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• 2010

Inflammatory reactology has become increasingly important in diabetic kidney disease. In this study, we estabilished STZ-induced diabetic rat model to investigate whether dendritic cells (DCs) mediated tubulointerstitial damages, and whether the effects by DCs were mediated by P-selectin expression and can be inhibited by atorvastatin. The study demonstrated that there was an accumulation of DCs in diabetic rats mediated by P-selectin. It also showed the accumulation of DCs and expression of P-selectin was closely correlated with the degree of renal tubulointerstitial injury. These effects were markedly attenuated by atorvastatin. Thus, DCs play a role in tubulointerstitial damages, atorvasttin can prevent renal tubulointerstitium from damage by inhibiting the P-selectin expression and DCs migration.

• Journal of the Korean Society of Food Culture
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• v.22 no.1
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• pp.140-148
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• 2007

Diabetic nephropathy has been increasing, although blood glucose and blood pressure can be controlled by angiotensin converting enzyme(ACE) or advanced glycosylation end products(AGE) inhibitors in the diabetic patients. We investigated the effect of dietary supplementation of sea tangle on the blood glucose, and pathological scoring of diabetic kidneys in the streptozotocin(STZ) induced diabetic rats. Male Sprague-Dawley rats were divided into normal rats fed control diet and diabetic rats fed control diet or control diet supplemented with powder or oater extract of sea tangle. Diabetes was induced by a single injection of STZ(60mg/kg, ip) in citrate buffer. The animals were fed the experimental diet and water for 13 weeks. Dietary supplementation of sea tangle decreased blood glucose in the diabetic rats. However, dietary supplementation of sea tangle did not affect the antioxidant enzyme activities, MDA content and pathology of diabetic kidneys. These results indicate that decreased blood glucose by sea tangle could not delay the progression of diabetic kidney disease.

• 한국생물공학회:학술대회논문집
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• 2005.10a
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• pp.839-840
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• 2005

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.385-390
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• 2010

Excessive extracellular matrix (ECM) accumulation is the main feature of chronic renal disease including diabetic nephropathy. Plasminogen activator inhibitor (PAI)-1 is known to play an important role in renal ECM accumulation in part through suppression of plasmin generation and matrix metalloproteinase (MMP) activation. The present study examined the effect of PAI-1 antisense oligodeoxynucleotide (ODN) on fibronectin upregulation and plasmin/MMP suppression in primary mesangial cells cultured under high glucose (HG) or transforming growth factor (TGF)-${\beta}1$, major mediators of diabetic renal ECM accumulation. Growth arrested and synchronized rat primary mesangial cells were transfected with $1\;{\mu}M$ phosphorothioate-modified antisense or control mis-match ODN for 24 hours with cationic liposome and then stimulated with 30 mM D-glucose or 2 ng/ml TGF-${\beta}1$. PAl-1 or fibronectin protein was measured by Western blot analysis. Plasmin activity was determined using a synthetic fluorometric plasmin substrate and MMP-2 activity analyzed using zymography. HG and TGF-${\beta}1$ significantly increased PAI-1 and fibronectin protein expression as well as decreased plasmin and MMP-2 activity. Transient transfection of mesangial cells with PAI-1 antisense ODN, but not mis-match ODN, effectively reversed basal as well as HG- and TGF-${\beta}1$-induced suppression of plasmin and MMP-2 activity. Both basal and upregulated fibronectin secretion were also inhibited by PAI-1 antisense ODN. These data confirm that PAI-1 plays an important role in ECM accumulation in diabetic mesangium through suppression of protease activity and suggest that PAI-1 antisense ODN would be an effective therapeutic strategy for prevention of renal fibrosis including diabetic nephropathy.

• Genomics & Informatics
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• v.20 no.3
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• pp.26.1-26.19
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• 2022

Diabetes and its related complications are associated with long term damage and failure of various organ systems. The microvascular complications of diabetes considered in this study are diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. The aim is to identify the weighted co-expressed and differentially expressed genes (DEGs), major pathways, and their miRNA, transcription factors (TFs) and drugs interacting in all the three conditions. The primary goal is to identify vital DEGs in all the three conditions. The overlapped five genes (AKT1, NFKB1, MAPK3, PDPK1, and TNF) from the DEGs and the co-expressed genes were defined as key genes, which differentially expressed in all the three cases. Then the protein-protein interaction network and gene set linkage analysis (GSLA) of key genes was performed. GSLA, gene ontology, and pathway enrichment analysis of the key genes elucidates nine major pathways in diabetes. Subsequently, we constructed the miRNA-gene and transcription factor-gene regulatory network of the five gene of interest in the nine major pathways were studied. hsa-mir-34a-5p, a major miRNA that interacted with all the five genes. RELA, FOXO3, PDX1, and SREBF1 were the TFs interacting with the major five gene of interest. Finally, drug-gene interaction network elucidates five potential drugs to treat the genes of interest. This research reveals biomarker genes, miRNA, TFs, and therapeutic drugs in the key signaling pathways, which may help us, understand the processes of all three secondary microvascular problems and aid in disease detection and management.

• Korean Journal of Pharmacognosy
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• v.37 no.2 s.145
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• pp.103-109
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• 2006

Advanced glycation end products (AGEs) formation plays an important role in the progression of diabetic complications. To develop effective herbal formulations with suppression of diabetic nephropathy, a common complication in diabetic patients, we evaluated inhibitory activities of KIOM-79, a new herbal prescription, on the formation of AGEs using in vitro and in vivo model systems. Effects of KIOM-79 on the expression of AGEs, RAGEs (receptor for Advanced glycation end products), type IV collagen and renal $TGF-{\beta}1$ mRNA was also examined in streptozotocon (STZ)-induced diabetic rats. STZ-induced diabetic rats were treated orally with KIOM-79 (250 and $500\;kg^{-1}$ once a day for 13 weeks). In vitro system KIOM-79 suppressed the formation of AGEs $(18.12\;{\mu}g/ml)$. In STZ-induced diabetic rats showing accumulation of AGE and RAGE, pathological examination revealed that KIOM-79 prevented AGE and RAGE deposition in the kidney. In STZ induced diabetic rats, the expansion of mesangial matrix and the glomerular tufts seemed to be larger than those in normal rats. Howεver, after administration with KIOM-79, mesangial metrix and glomerular volume were decreased, and overexpression of type IV collagen was also decreased. Overexpression of renal $TGF-{\beta}1$ mRNA was inhibited significantly. These results suggest that the KIOM-79 might be an effective herbal prescription to prevent or alleviate the progression of diabetic nephropathy.