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ABSTRACT: Apigenin promotes apoptosis in cancer cells. We studied the effect of apigenin on cell survival and c-Myc expression in FRO anaplastic thyroid carcinoma (ATC) cells. Apigenin caused apoptosis via the elevation of c-Myc levels in conjunction with the phosphorylation of p38 and p53. In the c-myc siRNA-transfected and apigenin-treated cells, compared with the apigenin-treated control cells, apoptosis and phosphorylation of p38 and p53 were ameliorated. In the presence of apigenin, diminution of p38 and p53 did not affect cell survival although apigenin activated the phosphorylation of p38 and p53 via increased c-Myc levels. In conclusion, our results indicate that apigenin induces apoptosis mediated via c-Myc with concomitant phosphorylation of p53 and p38 in FRO ATC cells. These findings suggest that augmented c-Myc acts as a core regulator and is necessary for apigenin-induced apoptosis in FRO ATC cells.
Molecular and Cellular Endocrinology 01/2013; · 4.19 Impact Factor
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ABSTRACT: Glucagon-like peptide-1 (GLP-1) stimulates cell proliferation and has anti-apoptotic effects on pancreatic islet β cells. In our previous study, the transduction of mouse islets with a recombinant adenovirus containing GLP-1 cDNA enhanced islet graft survival. In this study, we sought to deliver the GLP-1 gene using a nonviral vector, which raises fewer safety issues in clinical application. We constructed a plasmid, pβ-SP-GLP-1, in which a secretion signal peptide (SP) was inserted to increase GLP-1 secretion, and transfected mouse islets using the nonviral carrier Effectene. Transfection of pβ-SP-GLP-1 induced a significant increase in bioactive GLP-1 levels in islet cultures. Islets transfected with pβ-SP-GLP-1 were protected from H(2) O(2) -induced cell damage in vitro. In addition, glucose-stimulated insulin secretion was significantly increased in pβ-SP-GLP-1-transfected islets. Diabetic syngeneic mice transplanted under the kidney capsule with a marginal mass of pβ-SP-GLP-1-transfected islets rapidly became normoglycemic, with 88% of recipients being normoglycemic at 30 days post-transplantation compared with 52% of mice that received pβ-transfected islet grafts (P < 0.05). Islet grafts retrieved 7 days after transplantation revealed that the pβ-SP-GLP-1-transfected group had significantly more Ki67-positive cells as compared with the pβ-transfected group. In conclusion, delivery of a plasmid containing a secretion SP and GLP-1 cDNA using a nonviral carrier leads to efficient secretion of GLP-1 in mouse islet cells, enhances islet cell survival during the early post-transplant period, and improves islet transplantation outcome.
Transplant International 01/2013; · 2.92 Impact Factor
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ABSTRACT: This study investigated the effect of local glucagon-like peptide-1 (GLP-1) production within mouse islets on cytoprotection in vitro and in vivo by gene transfer of GLP-1. Transduction of recombinant adenovirus vector expressing GLP-1 (rAd-GLP-1) induced a significant increase in bioactive GLP-1 in the mouse islet culture, whereas transduction with adenovirus vector expressing β-galactosidase (rAd-LacZ), as a control, had no effect on GLP-1 secretion. Islets transduced with rAd-GLP-1 were protected from H(2) O(2) -induced cell damage in vitro. In addition, glucose-stimulated insulin secretion was significantly increased in rAd-GLP-1-transduced islets. When transplanted under the kidney capsule of diabetic syngeneic mice, islet grafts retrieved 4 or 7 days after transplantation revealed that the rAd-GLP-1-transduced group had significantly more Ki67-positive cells as compared with the rAd-LacZ-transduced group. Regarding blood glucose control, diabetic mice transplanted with a marginal mass of rAd-GLP-1-transduced islets became normoglycemic more rapidly and 78% of the recipients were normoglycemic at 35 days post-transplant, whereas only 48% of the mice transplanted with rAd-LacZ-transduced islets were normoglycemic (P < 0.05). In conclusion, delivery of the GLP-1 gene to islets enhanced islet cell survival during the early post-transplant period, and preserved islet mass and functions over time in the transplants.
Transplant International 12/2011; 25(2):242-9. · 2.92 Impact Factor
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ABSTRACT: For gene transfer strategies to improve islet engraftment, vascular endothelial growth factor (VEGF) expression should be regulated in a way that matches the transient nature of revascularization with simultaneously avoiding undesirable effects of overexpression. The aim of this study was to investigate the effects of hypoxia-inducible VEGF gene transfer using the RTP801 promoter on islet grafts. We implanted pSV-hVEGF transfected, pRTP801-hVEGF transfected or nontransfected mouse islets under the kidney capsule of streptozotocin-induced diabetic syngeneic mice. Human VEGF immunostaining of day 3 grafts revealed that the pRTP801-hVEGF transfected group had higher hVEGF expression compared with the pSV-hVEGF transfected group. BS-1 staining of day 3 grafts from the pRTP801-hVEGF transfected group showed the highest vascular density, which was comparable with day 6 grafts from the nontransfected group. In 360 islet equivalent (IEQ)-transplantation which reverted hyperglycemia in all mice, the area under the curve of glucose levels during intraperitoneal glucose tolerance test 7 weeks post-transplant was lower in mice transplanted with pRTP801-hVEGF transfected grafts compared with mice transplanted with nontransfected grafts. In 220 IEQ-transplantations, diabetic mice transplanted with pRTP801-hVEGF islets became normoglycemic more rapidly compared with mice transplanted with pSV-hVEGF or nontransfected islets, and diabetes reversal rate after 50 days was 90%, 68%, and 50%, respectively. In conclusion, our results indicate that regulated overexpression of hVEGF in a hypoxia-inducible manner enhances islet vascular engraftment and preserves islet function overtime in transplants.
Transplant International 03/2011; 24(3):307-14. · 2.92 Impact Factor
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ABSTRACT: Activation of the receptor for advanced glycation endproducts (RAGE) by its ligands leads to cellular damage contributing to diabetic complications. It is not clearly known whether RAGE ligands influence pancreatic β-cells. In this study, we investigated the expression of RAGE in islet cells and the effect of RAGE ligands, S100b and HMG-1, on islet cells. RAGE was expressed in INS-1 cells and isolated rat and human islets at mRNA and protein levels. RAGE and its ligand, S100b, were detected on islet cells in 28-week-old diabetic OLETF rats. Both S100b and HMG-1 induced apoptotic cell death of INS-1 and islet cells. This INS-1 cell apoptosis was accompanied by increased intracellular oxidative stress and inhibited by antioxidants or a NADPH oxidase inhibitor. Our results showing S100b/RAGE expression on islets of diabetic rat model and RAGE ligands-induced islet cell apoptosis via NADPH oxidase-mediated ROS generation suggest that RAGE ligands-RAGE interaction may contribute not only to the development of diabetic complications but also to the progressive β-cell loss in type 2 diabetes by inducing oxidative stress.
International Journal of Molecular Medicine 12/2010; 26(6):813-8. · 1.98 Impact Factor
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ABSTRACT: We designed a system for diabetes patients treated with glargine, a long-acting insulin, to make an automatic adjustment of insulin dose based on glucose level data and to provide the patients with the needed insulin dose by using a short message service (SMS). We also compared diabetes patients who used our system with patients who received the conventional titration scheme.
Included were 100 type 2 diabetes patients whose blood glucose was suboptimally controlled on their previous antidiabetes treatment. Each participant was assigned to either the intervention or control group, each with 50 patients, using adaptive randomization. We applied our system to the intervention group for 12 weeks, whereas the control group received a conventional titration scheme, seeking a target fasting blood glucose of <120 mg/dL.
The fasting and postprandial glucose levels of the intervention group declined earlier than those of the control group. Lastly, a greater (P = 0.023) reduction in hemoglobin A(1C) from baseline to the end point was observed in the intervention group (from 9.8 +/- 1.3% to 7.4 +/- 0.7%) than in the control group (from 9.8 +/- 1.2% to 7.8 +/- 0.8%). The incidence of symptomatic, asymptomatic, and nocturnal hypoglycemia was similar in both groups. There was a small increase in body weight from baseline to the end point with both the intervention (2.4 +/- 3.0 kg) and control (2.2 +/- 2.8 kg) groups.
This study demonstrated that SMS based on our specialized Internet-supported system is an effective and safe approach to long-acting insulin dose adjustments in patients with type 2 diabetes.
Diabetes Technology & Therapeutics 08/2010; 12(8):663-9. · 1.93 Impact Factor
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Chul Sik Kim,
So Young Park,
Sung Hoon Yu,
Jun Goo Kang,
Ohk Hyun Ryu,
Seong Jin Lee,
Eun Gyung Hong,
Hyeon Kyu Kim,
Doo-Man Kim,
Jae Myung Yoo, Sung Hee Ihm,
Moon Gi Choi,
Hyung Joon Yoo
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ABSTRACT: Little is known about the relative contribution of long-term glycemic variability to the risk of macrovascular complications in type 2 diabetes. This study was conducted to evaluate the effect of A1C variability on the progression of carotid artery intima-media thickness (IMT) in type 2 diabetic patients.
Among type 2 diabetic patients who visited Hallym University Sacred Heart Hospital from March 2007 to September 2009, 120 patients who had carotid artery IMT measured annually and A1C checked every three months for at least one year were analyzed. Individual A1C variability was defined as the standard deviation (SD) of five A1C levels taken every three months for approximately one year. Change in IMT was defined as an increase in IMT on follow-up measurement. The association between the SD of A1C and changes in IMT was evaluated.
With greater A1C variability, there was a greater increase in the mean IMT (r = 0.350, P < 0.001) of the carotid artery. After adjusting for confounding factors that may influence IMT, A1C variability was significantly associated with the progression of IMT (r = 0.222, P = 0.034). However, the SD of A1C was not a significant independent risk factor for the progression of IMT in multiple regression analysis (beta = 0.158, P = 0.093).
Higher A1C variability is associated with IMT progression in type 2 diabetic patients; however, it is not an independent predictor of IMT progression. Overall glycemic control is the most important factor in the progression of IMT.
Korean Diabetes Journal 06/2010; 34(3):174-81.
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Jun Goo Kang,
Cheol-Young Park, Sung-Hee Ihm,
Hyung Joon Yoo,
Heesoon Park,
Eun Jung Rhee,
Jong Chul Won,
Won Young Lee,
Ki Won Oh,
Sung Woo Park,
Sun Woo Kim
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ABSTRACT: Treatment with thiazolidinediones (TZDs) improves glucose homeostasis by increasing insulin sensitivity, but it also leads to weight gain. Our hypothesis was that, in individual adipose depots, there is depot specificity for lipid storage and energy expenditure genes after TZD treatment. After 5 weeks of rosiglitazone treatment on Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes mellitus with obesity, and Long-Evans Tokushima Otsuka rats as controls, we measured changes in lipid storage and energy expenditure gene expression in various adipose depots, such as mesenteric and nonmesenteric adipose tissues (subcutaneous, epididymal, and retroperitoneal). Mesenteric fat masses did not change after TZD treatment in OLETF rats, but nonmesenteric fat masses increased. Messenger RNA expression of lipid storage genes increased in nonmesenteric fat, but energy expenditure gene expression increased in mesenteric fat after rosiglitazone treatment. In conclusion, our findings suggest that TZD treatment may be associated with the depot-specific effects of lipid storage and energy expenditure genes on fat redistribution in individual adipose tissues in OLETF rats.
Metabolism: clinical and experimental 09/2009; 59(1):46-53. · 2.59 Impact Factor
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ABSTRACT: Although non-viral vectors are relatively safe, they have very low gene transfection efficiency, especially in pancreatic islet cells. To provide information on the use of non-viral vectors for transfecting genes into pancreatic islet cells, a comparative evaluation of non-viral options was performed. In vitro experiments were used to compare the transfection efficiency of three classes of non-viral vectors: Effectene, polyethylenimine (PEI, 25 kDa) and hemagglutinating virus of Japan-envelope (HVJ-E), into insulinoma cells (INS-1) and rat islets. Vascular endothelial growth factor (VEGF) gene with hypoxia-inducible RTP801 promoter was delivered into rat islets with Effectene and VEGF secretion under hypoxia was measured in the culture media. Luciferase activity and GFP assays indicated that Effectene exhibited the highest transfection efficiency, and HVJ-E was not suitable for transfection into pancreatic beta-cells. The cytotoxicity of Effectene was found to be similar to that of 25-kDa PEI by 7-amino actinomycin D (7-AAD) flow cytometry and acridine orange/propidium iodide (AO/PI) assays. When RTP801 promoter-VEGF plasmid was delivered to rat islets with Effectene, VEGF secretion increased specifically in islets under hypoxia. In conclusion, Effectene showed higher gene-delivery efficiency for pancreatic islets compared with other classes of non-viral delivery systems and is promising as a gene delivery agent for pretransplant ex vivo gene therapy of islets.
International Journal of Molecular Medicine 07/2009; 23(6):757-62. · 1.98 Impact Factor
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ABSTRACT: In diabetic nephropathy, transforming growth factor beta1 (TGFbeta1) is related to p38 mitogen-activated protein kinase (MAPK) that induces production of fibronectin in mesangial cells. We investigated the effects of alpha-lipoic acid (ALA), a potent antioxidant, on proteinuria and TGFbeta1-p38 MAPK-fibronectin pathway in diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. After ALA treatment for 5 weeks in OLETF rats at 30 weeks of age, plasma malondialdehyde, urinary protein excretion, renal cortical TGFbeta1, and fibronectin protein levels were decreased; and urinary protein excretion was positively correlated with renal cortical TGFbeta1 and fibronectin protein levels. Phospho-form but not total-form levels as well as fold activations of each protein consisting of p38 MAPK pathway were also attenuated. These results suggest that ALA ameliorates proteinuria by attenuating expressions of TGFbeta1 and fibronectin proteins, and these favorable effects are related to inhibition of phosphorylating activation of p38 MAPK pathway in renal cortex of OLETF rats.
Metabolism: clinical and experimental 06/2009; 58(5):616-23. · 2.59 Impact Factor
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ABSTRACT: In this study, we developed an expression system of exendin-4, a glucagon-like peptide (GLP-1) analog, using a secretion signal peptide (SP) to facilitate exendin-4 secretion. For delivery of the exendin-4 expression system, high-molecular-weight polyethylenimine (25 kDa, PEI25k), low-molecular-weight polyethylenimine (2 kDa, PEI2k), and polyamidoamine (PAMAM) dendrimers were evaluated as gene carriers to Ins-1 beta cells. As a result, PEI25k showed the highest transfection efficiency. For the construction of the exendin-4 expression vector, DNA coding the SP sequence was inserted upstream of the exendin-4 cDNA, resulting in the construction of pbeta-SP-Ex-4. Transfection assay showed that the secretion level of exendin-4 increased in the pbeta-SP-Ex-4 transfected cells, compared with the pbeta-Ex-4 transfected cells. To identify the beta-cell protection effect of pbeta-SP-Ex-4 delivery, the Ins-1 beta cells were transfected with pbeta-SP-Ex-4 or pbeta-Ex-4 and incubated under normoxia or hypoxia. An MTT assay showed that the pbeta-SP-Ex-4 transfected cells had higher beta-cell viability than the pbeta-Ex-4 transfected cells under hypoxia. In addition, the pbeta-SP-Ex-4 transfected cells exhibited lower caspase-3 activity than the pbeta-Ex-4 transfected cells. Therefore, PEI25k/pbeta-SP-Ex-4 complex may be useful to protect isolated beta cells from apoptosis during transplantation.
Journal of Drug Targeting 05/2009; 17(3):242-8. · 2.70 Impact Factor
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ABSTRACT: This study aimed to investigate thyroid hormone (TH) status and its relationship with myocardial function as well as clinical and biochemical parameters in stress cardiomyopathy (CMP).
Forty-five patients with stress CMP (the patient group), 31 patients without stress CMP (the control II group), and 58 healthy subjects (the control I group) were included. Sick euthyroid syndrome (SES) was defined as low total triiodothyronine (T(3)) with normal TSH levels.
In the patient group at admission, prevalence of SES was 62.2%. Compared with the control I group, the patient group had a decrease in left ventricular ejection fraction (LVEF) and systolic blood pressure (BP) and an increase in troponin-I, CK-MB, and B-type natriuretic peptide (BNP) levels. Total T(3) levels were reduced, and anti-thyroid peroxidase antibody (anti-TPO Ab) positivity, C-reactive protein (CRP) and cortisol levels were elevated. Total T(3) levels were associated with acute physiology and chronic health evaluation II (APACHE II) score, LVEF, systolic BP, and cortisol levels in multivariate analysis. In the control II group, total T(3) levels were not associated with any variables. In the SES (n=28) and myocardial dysfunction (MDys, n=27) subgroups, increased APACHE II score and BNP levels as well as decreased LVEF and systolic BP were significant. Total T(3) levels were reduced, and CRP, cortisol and catecholamines levels were elevated. In the MDys subgroup, anti-TPO Ab positivity and titer were increased.
These results suggest that total T(3) levels may be associated with myocardial contractility, clinical severity, and cortisol levels. Thyroid autoimmunity may influence myocardial contractility in stress CMP.
European Journal of Endocrinology 03/2009; 160(5):799-806. · 3.42 Impact Factor
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ABSTRACT: alpha-Lipoic acid (alpha-LA), an antioxidant used for diabetic polyneuropathy, was reported to induce AMP-activated protein kinase activation and reductions in insulin secretion in pancreatic beta-cells at high concentrations (> or = 500 micromol/l). This study investigated whether alpha-LA has a protective role under oxidative stress in beta-cells and its effect is dose-related. In INS-1 cells treated with alpha-LA (150-1200 micromol/l) for 24 h, alpha-LA itself (> or = 300 micromol/l) induced apoptotic death dose-dependently. However, pre-treatment with 150 and 300 micromol/l alpha-LA reduced the hydrogen peroxide-induced apoptosis in INS-1 cells and isolated islets. alpha-LA alleviated hydrogen peroxide-induced reactive oxygen species production, mitochondrial membrane depolarization and c-JNK activation in beta-cells. alpha-LA induced phosphoinositide 3-kinase-dependent Akt phosphorylation in INS-1 cells. While alpha-LA is harmful to beta-cells at high concentrations in vitro, it has potential cytoprotective effects on beta-cells under oxidative stress as in diabetes by its antioxidant properties and possibly by Akt phosphorylation at clinically relevant concentrations.
Free radical research 02/2009; 43(1):68-77. · 2.22 Impact Factor
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ABSTRACT: Islet transplantation is a promising strategy for treatment of diabetes. However, islets are exposed to hypoxia in the process of isolation and transplantation and prone to apoptosis. Vascular endothelial growth factor (VEGF) gene transfer is one of the promising strategies to address this problem. However, VEGF expression in the cells under normoxia is undesirable since it may induce pathological angiogenesis. Therefore, VEGF expression should be regulated to avoid this problem. In this study, hypoxia-inducible VEGF gene was transferred to islets using a non-viral carrier. Rat islets were transfected with high molecular weight PEI (25 kDa, PEI25K), low molecular weight PEI (2 kDa, PEI2K), and polyamidoamine dendrimer (PAMAM). PEI25K had higher transfection efficiency to rat islets than PAMAM or PEI2K. The hypoxia-inducible gene expression vector, pRTP801-Luc or pRTP801-VEGF was transferred to rat islets using PEI25K. Transfection assay with pRTP801-Luc showed that luciferase expression was induced in rat islets under hypoxia. In addition, transfer of pRTP801-VEGF showed that VEGF gene expression was higher under hypoxia than normoxia in rat islets. In conclusion, delivery of pRTP801-VEGF using PEI25K induces VEGF level specifically under hypoxia and may be useful for the development of anti-apoptotic strategies for islet transplantation.
Journal of Drug Targeting 02/2009; 17(1):1-9. · 2.70 Impact Factor
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ABSTRACT: The Edmonton protocol for islet transplantation utilizes fresh islet grafts but other protocols increasingly transplant short-term cultured grafts mainly for practical reasons. To improve our understanding of the impact of culture pretreatment of human islets, we assessed post-transplant function by nude mouse bioassay, islet ATP, activity of stress-activated MAP kinases, and expression of stress-related genes by focused cDNA array in freshly isolated and cultured islets. Mean blood glucose levels over 4 weeks after transplantation (2000 IE) of (i) freshly isolated, (ii) cultured and preculture counted (recovery rate; 78 +/- 6%), and (iii) cultured and postculture counted islets in diabetic mice were 330 +/- 40, 277 +/- 65, and 256 +/- 52 mg/dl (i versus ii, P = 0.004; i versus iii, P = 0.002). During culture, islet ATP/DNA and ATP/ADP increased; JNK and p38 MAPK activities decreased. Among 96 genes studied, mRNA expression of heat shock protein 70 genes decreased >twofold during culture in all four pairs; expression of cyclooxygenase-2, superoxide dismutase-2, interleukin-6 and cytochromes P450 1A1 genes increased. Our results show that culturing human islets before transplantation is not disadvantageous in regard of functional recovery from changes induced by nonphysiologic stimuli during islet isolation. The increase in expression of several stress-related genes during culture also shows that improving culture conditions may further enhance post-transplant islet function.
Transplant International 10/2008; 22(2):207-16. · 2.92 Impact Factor
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ABSTRACT: Dyslipidaemia is a well-known manifestation of thyroid dysfunction. Recently, small low-density lipoprotein (LDL) particle size has been linked with development of cardiovascular disease. To better understand the effects of thyroid dysfunction on the development of cardiovascular disease, we examined LDL particle size and lipid profiles in subjects with different thyroid function.
Included were 46 patients with overt hypothyroidism, 57 patients with subclinical hypothyroidism, 46 patients with overt hyperthyroidism, 51 patients with subclinical hyperthyroidism, and 110 age- and sex-matched healthy control subjects. We measured LDL particle size and lipid profiles in these subjects.
No significant differences were found in LDL particle size between the groups with different thyroid function. Serum total cholesterol and LDL-cholesterol levels were significantly higher in the cases of hypothyroidism than in the cases of hyperthyroidism and the healthy control subjects. Serum triglyceride levels were higher in subjects with overt hypothyroidism than in those with overt hyperthyroidism or healthy control subjects.
LDL particle size, the emerging risk factor for atherosclerosis, did not appear to be significantly affected by the degree of thyroid dysfunction. Increased risk of atherosclerosis in hypothyroidism does not appear to be associated with LDL particle size, the non-traditional cardiovascular risk factor.
Clinical Endocrinology 10/2008; 71(1):130-6. · 3.17 Impact Factor
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ABSTRACT: Patients with thymoma are likely to present with associated autoimmunologic disorders. The occurrence of syndrome of inappropriate antidiuretic hormone (SIADH) attributable to thymoma is extremely rare. We herein present an extremely rare case of a 59-year-old man patient who was discovered to have malignant thymoma associated with myasthenia gravis, Graves' disease, and SIADH. He was admitted for evaluation and treatment of hyponatremia (Na 125 mEq/l). SIADH was diagnosed, and thymoma was identified as its cause. The patient was also found to have both Graves' disease and myasthenia gravis. The hyponatremia was normalized with water restriction and 3% saline therapy before thymectomy. The thymic tumor was a Masaoka stage III thymoma that resulted in direct invasion to the wall of the innominate vein, but there was no finding of invasion to other mediastinal organs. Complete thymectomy with innominate vein graft was performed. Microscopic histopathology findings corresponded to those of a mixed-type thymoma and type B2. However, immunohistochemical stain for antidiuretic hormone was negative in the tumor cells. Adjuvant radiation therapy was employed postoperatively, and the patient's postoperative recovery was uneventful. He subsequently reached a euthyroid state. And the reversal to normal sodium and osmolality levels was continued after the tumor removal without any further management for hyponatremia. The observation of this interesting case and a literature review provided us with the opportunity to explore the pathogenesis and clinical aspects of thymoma-related autoimmune and/or endocrine disorders which must be suspected in patients with thymoma.
Internal Medicine 01/2008; 47(11):1009-12. · 0.94 Impact Factor
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ABSTRACT: In a clinic-based, cross-sectional study of 320 type 2 diabetic patients, we staged the level of diabetic nephropathy (normoalbuminuric, microalbuminuric and macroalbuminuric stage) and estimated GFR based on serum creatinine and cystatin C (CysC). Serum creatinine and CysC levels were 0.91+/-0.21 mg/dL and 0.87+/-0.26 mg/L, respectively. Correlation coefficients between CysC-GFR and each of the creatinine-based GFR measurements (MDRD-GFR, Cockcroft-Gault-GFR, and CLcr) were 0.589, 0.569, and 0.479 (p<0.001). Serum CysC was significantly lower in normoalbuminurics (0.83+/-0.22) than in microalbuminurics and macroalbuminurics (0.94+/-0.33 and 1.05+/-0.28; p=0.004 and p<0.001). Of the estimations of GFR, significant differences among the groups were found on CysC-GFR and CLcr. CysC-GFR (mL/min) was statistically lower in macroalbuminurics (79.5+/-30.5) than in normoalbuminurics (104.3+/-30.9, p=0.01). The logistic regression analyses showed that retinopathy, A1C, CysC, diabetic duration, and CysC-GFR were indicators to predict the development of microalbuminuria. Serum CysC seems to be more accurate serum marker than serum creatinine in evaluating a prognostic stage of type 2 diabetic nephropathy. Our study suggests that, in Korean type 2 diabetic patients, CysC-based GFR might be more valuable than creatinine-based GFR in the prediction of the microalbuminuric stage.
Diabetes research and clinical practice 12/2007; 78(3):428-34. · 2.16 Impact Factor
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ABSTRACT: Recently, the glucose-stimulated insulin release of isolated human islets has been shown to deteriorate progressively with advancing donor age. This decline in beta cell function with aging may contribute to the increasing development of IGT and type 2 diabetes and also to the progressive nature of the disease. This study was to see whether there is any change in expression of beta cell function-related genes in islets with aging. Islets were isolated from young (2-month old) and old (22-24-month old) LETO rats and C57BL/6N mice. The in vitro GSIR index was significantly lower in islets from old mice compared with young mice. In real-time RT-PCR, PDX-1, insulin, GLUT2 and prohormone convertase 1/3 gene expression in islets was markedly lower in old rats (33%, 13%, 20% and 34%, respectively) and old mice (56%, 42%, 28% and 22%, respectively) compared with young animals. On the other hand, genes not specifically related to beta cell-specific function, such as caspase 3, superoxide dismutase 2 and glycerol kinase were not significantly different in expression in islets according to age. In conclusion, with increasing age, insulin secretory function of islets deteriorates accompanied with a decrease in expression of beta cell-specific genes including PDX-1.
Diabetes Research and Clinical Practice 10/2007; 77 Suppl 1:S150-4. · 2.75 Impact Factor
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ABSTRACT: We investigated the effects of Amadori-glycated serum albumin (GSA) on cell proliferation as well as expressions of antioxidant enzyme genes and marker genes associated with signal transduction pathways in rat aortic vascular smooth muscle cells (VSMCs). Quiescent VSMCs treated with GSA (0-500 microg/mL, 48 h) exhibited a dose-dependent increase in proliferation that was prevented by PD98059 (25 microM), suggesting a MAPK-dependent signaling pathway. Compared with bovine serum albumin (BSA)-treated cells, the GSA (500 microg/mL, 24~h)-treated VSMCs showed a higher superoxide dismutase 2 gene expression in quantitative RT-PCR, suggesting the involvement of oxidative stress. In a focused oligonucleotide array containing 96 signal transduction-related genes, expression of inhibitor of apoptosis protein-1 (IAP-1), nerve growth factor-gamma (NGF-gamma), and c-jun genes was significantly higher in the GSA-treated VSMCs. These results suggest that induction of antiapoptotic proteins like IAP-1 and strong mitogens like NGF-gamma by GSA might further contribute to the VSMC proliferation and accelerated vascular remodeling in diabetes.
BioFactors 02/2007; 31(3-4):145-53. · 4.93 Impact Factor
