Woo Je Lee

Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib and sunitinib

Summary Background  The multitargeted kinase inhibitors sorafenib and sunitinib have improved treatment of solid tumours including renal cell carcinoma and hepatocellular carcinoma by offering better clinical responses. However, sorafenib and sunitinib are commonly associated with cutaneous toxicity.

Effects of Recombinant Adenovirus-Mediated Uncoupling Protein 2 Overexpression on Endothelial Function and Apoptosis

Increased oxidative stress in vascular cells plays a key role in the development of endothelial dysfunction and atherosclerosis. Uncoupling protein 2 (UCP2) is an important regulator of intracellular reactive oxygen species (ROS) production. This study was undertaken to test the hypothesis that, UCP2 functions as an inhibitor of the atherosclerotic process in endothelial cells. Adenovirus-mediated UCP2 (Ad-UCP2) overexpression led to a significant increase in endothelial nitric oxide synthase (eNOS) and decrease in endothelin-1 mRNA expression in human aortic endothelial cells (HAECs). Moreover, UCP2 inhibited the increase in ROS production and NF-&kgr;B activation, and apoptosis of HAECs induced by lysophophatidylcholine (LPC) and linoleic acid. LPC and linoleic acid caused mitochondrial calcium accumulation and transient mitochondrial membrane hyperpolarization, which was followed by depolarization. UCP2 overexpression prevented these processes. In isolated rat aorta, Ad-UCP2 infection markedly improved impaired vascular relaxation induced by LPC. The data collectively suggest that UCP2, functions as a physiologic regulator of ROS generation in endothelial cells. Thus, measures to increase UCP2 expression in vascular endothelial cells may aid in preventing the development and progression of atherosclerosis in patients with metabolic syndrome.

α-Lipoic Acid Prevents Endothelial Dysfunction in Obese Rats via Activation of AMP-Activated Protein Kinase

Objective—Lipid accumulation in vascular endothelial cells may play an important role in the pathogenesis of atherosclerosis in obese subjects. We showed previously that α-lipoic acid (ALA) activates AMP-activated protein kinase (AMPK) and reduces lipid accumulation in skeletal muscle of obese rats. Here, we investigated whether ALA improves endothelial dysfunction in obese rats by activating AMPK in endothelial cells. Methods and Results—Endothelium-dependent vascular relaxation was impaired, and the number of apoptotic endothelial cells was higher in the aorta of obese rats compared with control rats. In addition, triglyceride and lipid peroxide levels were higher, and NO synthesis was lower. Administration of ALA improved all of these abnormalities. AMPK activity was lower in aortic endothelium of obese rats, and ALA normalized it. Incubation of human aortic endothelial cells with ALA activated AMPK and protected cells from linoleic acid–induced apoptosis. Dominant-negative AMPK inhibited the antiapoptotic effects of ALA. Conclusions—Reduced AMPK activation may play an important role in the genesis of endothelial dysfunction in obese rats. ALA improves vascular dysfunction by normalizing lipid metabolism and activating AMPK in endothelial cells.

Effect of cranberry extracts on lipid profiles in subjects with Type 2 diabetes

Aim  To examine the effect of cranberry ingestion on lipid profiles in Type 2 diabetic patients taking oral glucose‐lowering drugs.

Effects of Alpha-Lipoic Acid on Body Weight in Obese Subjects

PURPOSE alpha-lipoic acid is an essential cofactor for mitochondrial respiratory enzymes that improves mitochondrial function. We previously reported that alpha-lipoic acid markedly reduced body weight gain in rodents. The purpose of this study was to determine whether alpha-lipoic acid reduces body weight in obese human subjects. METHODS in this randomized, double-blind, placebo-controlled, 20-week trial, 360 obese individuals (body mass index [BMI] ≥ 30 kg/m(2) or BMI 27-30 kg/m(2) plus hypertension, diabetes mellitus, or hypercholesterolemia) were randomized to alpha-lipoic acid 1200 or 1800 mg/d or placebo. The primary end point was body weight change from baseline to end point. RESULTS the 1800 mg alpha-lipoic acid group lost significantly more weight than the placebo group (2.1%; 95% confidence interval, 1.4-2.8; P<.05). Urticaria and itching sensation were the most common adverse events in the alpha-lipoic acid groups, but these were generally mild and transient. CONCLUSION alpha-lipoic acid 1800 mg/d led to a modest weight loss in obese subjects. Alpha-lipoic acid may be considered as adjunctive therapy for obesity.

Contribution of postprandial glucose to excess hyperglycaemia in Asian type 2 diabetic patients using continuous glucose monitoring

Previous studies examining the contributions of fasting glucose (FG) and postprandial glucose (PPG) to glycated haemoglobin (

Vaspin protects vascular endothelial cells against free fatty acid-induced apoptosis through a phosphatidylinositol 3-kinase/Akt pathway.

\hbox{HbA}_{{\rm 1c}}

Association between birth weight and insulin sensitivity in healthy young men in Korea: role of visceral adiposity.

) have yielded conflicting results. We aimed to clarify the contributions of PPG to hyperglycaemia in Asian type 2 diabetic patients using continuous glucose monitoring.

Peroxisome Proliferator-Activated Receptor-γ Coactivator 1-α Overexpression Prevents Endothelial Apoptosis by Increasing ATP/ADP Translocase Activity

Vaspin, an adipocytokine recently identified in a rat model of type 2 diabetes, has been suggested to have an insulin-sensitizing effect. However, the exact mechanism underlying this action has not been fully elucidated. Furthermore, the specific function of vaspin is largely unknown, especially in vascular cells. We examined whether vaspin affects the insulin-signaling pathway in cultured endothelial cells and is capable of preventing free fatty acid (FFA)-induced apoptosis in endothelial cells through its insulin sensitizing effect, specifically, through its stimulatory effect on PI3-kinase/Akt signaling pathways. Vaspin significantly increased Akt phosphorylation and prevented the impairment of Akt phosphorylation by linoleic acid (LA) in insulin-stimulated endothelial cells, which effects were abolished by pretreatment with the PI3-kinase inhibitor, Wortmannin. Moreover, pretreatment with vaspin prevented LA-induced apoptosis in insulin-stimulated endothelial cells; this anti-apoptotic effect of vaspin was also eliminated by pretreatment with Wortmannin. The present study indicates that vaspin protects vascular endothelial cells from FFA-induced apoptosis through upregulation of the PI3-kinase/Akt signaling pathway. Our study is the first to demonstrate that vascular cells can be targets of vaspin. Our results further suggest that vaspin could have beneficial effects on the atherosclerosis.

Hormonal activity of AIMP1/p43 for glucose homeostasis

Recent studies have demonstrated decreased insulin sensitivity in individuals with low birth weight. This study was performed to examine whether abdominal obesity is a link between insulin resistance and low birth weight. We studied the relationships between birth weight and insulin secretion, insulin sensitivity, and various anthropometric indices including visceral fat area in 22 healthy young Korean adults. Birth weight correlated significantly with diastolic blood pressure (r=-0.47, P<0.05) and insulin sensitivity index (S(I)) measured by a frequently sampled intravenous glucose tolerance test (FSIGT) (r=0.54, P<0.05), but not with insulin secretory indices such as acute insulin responses during FSIGT (r=-0.35, NS) or hyperglycemic clamp (r=0.17, NS) and submaximum insulin response during hyperglycemic clamp (r=0.10, NS). S(I) correlated significantly with abdominal obesity measurements such as waist circumference (r=-0.48, P<0.05), waist-to-hip ratio (r=-0.53, P<0.05) and visceral fat area (r=-0.58, P<0.01). However, we could not find significant correlation between birth weight and any of the abdominal obesity measurements (r=-0.35 for waist-to-hip ratio, r=-0.22 for visceral fat area, and r=-0.24 for visceral-to-subcutaneous fat ratio; NS for all). The present data confirm that low birth weight is associated with insulin resistance in adult life. However, our data suggest that the association between low birth weight and insulin resistance is not mediated by abdominal obesity.