Autophagy is necessary for the degradation of long-lasting proteins and nonfunctional organelles, and is activated to promote cellular survival. However, overactivation of autophagy may deplete essential molecules and organelles responsible for cellular survival. Lifelong calorie restriction by 40% has been shown to increase the cardiac expression of autophagic markers, which suggests that it may have a cardioprotective effect by decreasing oxidative damage brought on by aging and cardiovascular diseases. Although cardiac autophagy is critical to regulating protein quality and maintaining cellular function and survival, increased or excessive autophagy may have deleterious effects on the heart under some circumstances, including pressure overload-induced heart failure. The importance of autophagy has been shown in nutrient supply and preservation of energy in times of limitation, such as ischemia. Some studies have suggested that a transition from obesity to metabolic syndrome may involve progressive changes in myocardial inflammation, mitochondrial dysfunction, fibrosis, apoptosis, and myocardial autophagy.
Aging ; Apoptosis ; Autophagy ; Cardiovascular Diseases ; Fibrosis ; Heart ; Heart Failure ; Inflammation ; Ischemia ; Nutritional Status ; Obesity ; Organelles ; Proteins ; Starvation

OBJECTIVE: Peroxisome proliferator-activated receptor delta (PPAR-delta) is an ubiquitously expressed nuclear receptor that has been implicated in adipose tissue formation, brain development, and atherosclerosis. Despite mouse studies demonstrating that PPAR-delta activation has favorable anti-atherogenic properties by improving systemic lipid profiles, the relationship between PPAR-delta agonist and angiogenesis is unknown. We hypothesized that PPAR-delta ligands modulate the angiogenesis. METHODS: To test this hypothesis we treated primary cultures of bovine aortic endothelial cells with PPAR-delta specific ligand, GW501516 (50-800 nM) for 6 h. RESULTS: GW501516 dose-dependently decreased nitric oxide production without alteration in endothelial nitric oxide synthase (eNOS) expression. Analysis with phospho-specific antibodies against eNOS demonstrated that GW501516 significantly decreased the phosphorylation of eNOS at Serine1179 (eNOS-Ser1179). Concurrently, GW501516 also decreased the Akt phosphorylation. GW501516 did not affect endothelial cell proliferation or induce apoptosis. However, GW501516 inhibited endothelial cell migration, and tube formation in a high nanomolar concentration. The inhibition of endothelial cell tube formation by GW501516 was prevented by addition of the nitric oxide donor, DETA NONOate (5 microM). GW501516 was also found to inhibit angiogenesis in vivo in the chicken chorioallantoic membrane assay. CONCLUSION: These results provide that high nanomolar range of GW501516 inhibits angiogenesis by a mechanism involving dephosphorylation of eNOS-Ser1179.
Adipose Tissue ; Animals ; Antibodies, Phospho-Specific ; Apoptosis ; Atherosclerosis ; Brain ; Chickens ; Chorioallantoic Membrane ; DEET ; Endothelial Cells ; Humans ; Ligands ; Mice ; Nitric Oxide ; Nitric Oxide Synthase Type III ; Nitroso Compounds ; Peroxisomes ; Phosphorylation ; PPAR delta ; Thiazoles ; Tissue Donors

No abstract available.
Obesity ; Tea

Critically ill patients often experience hyperglycemia, which may be associated with increased morbidity and mortality. In 2001, van den Berghe et al. suggested significant benefit of normalization of blood glucose level in critically ill patients using intensive intravenous insulin therapy. Subsequent multicenter randomized studies, however, demonstrated adverse effects of tight glucose control. Therefore, while the need for glucose control in critically ill patients is generally accepted, the treatment thresholds for initiation of insulin therapy or target glucose values are still undetermined. Furthermore, occurrence of a hypoglycemic event during intensive insulin therapy is known to be an independent predictor of clinical outcome, and glycemic variability is an important variable of glucose management in the critically ill patients. Novel technological approaches such as a continuous glucose monitoring system (CGMS) might help to overcome some problems of tight glucose control by reducing the risk of hypoglycemia and minimizing glycemic variability.
Blood Glucose ; Critical Illness* ; Glucose ; Humans ; Hyperglycemia ; Hypoglycemia ; Insulin ; Intensive Care Units ; Mortality

The global burden of diabetes mellitus and its related complications are currently increasing. Diabetes mellitus affects the heart through various mechanisms including microvascular impairment, metabolic disturbance, subcellular component abnormalities, cardiac autonomic dysfunction, and a maladaptive immune response. Eventually, diabetes mellitus can cause functional and structural changes in the myocardium without coronary artery disease, a disorder known as diabetic cardiomyopathy (DCM). There are many diagnostic tools and management options for DCM, although it is difficult to detect its development and effectively prevent its progression. In this review, we summarize the current research regarding the pathophysiology and pathogenesis of DCM. Moreover, we discuss emerging diagnostic evaluation methods and treatment strategies for DCM, which may help our understanding of its underlying mechanisms and facilitate the identification of possible new therapeutic targets.
Coronary Artery Disease ; Diabetes Mellitus ; Diabetic Cardiomyopathies* ; Heart ; Heart Failure ; Myocardium

Diabetic heart disease is a growing and important public health risk. Apart from the risk of coronary artery disease or hypertension, diabetes mellitus (DM) is a well-known risk factor for heart failure in the form of diabetic cardiomyopathy (DiaCM). Currently, DiaCM is defined as myocardial dysfunction in patients with DM in the absence of coronary artery disease and hypertension. The underlying pathomechanism of DiaCM is partially understood, but accumulating evidence suggests that metabolic derangements, oxidative stress, increased myocardial fibrosis and hypertrophy, inflammation, enhanced apoptosis, impaired intracellular calcium handling, activation of the renin-angiotensin-aldosterone system, mitochondrial dysfunction, and dysregulation of microRNAs, among other factors, are involved. Numerous animal models have been used to investigate the pathomechanisms of DiaCM. Despite some limitations, animal models for DiaCM have greatly advanced our understanding of pathomechanisms and have helped in the development of successful disease management strategies. In this review, we summarize the current pathomechanisms of DiaCM and provide animal models for DiaCM according to its pathomechanisms, which may contribute to broadening our understanding of the underlying mechanisms and facilitating the identification of possible new therapeutic targets.

Pregnant women with diabetes are at greater risk for adverse outcomes, such as miscarriage, macrosomia, and preterm birth. Advances in the care of diabetes have reduced maternal and perinatal mortality rates to the levels expected in nondiabetic pregnancies. Lifestyle modification such as medical nutritional therapy and exercise is a first step in therapy for gestational diabetes. Rapid-acting insulin analogs (lispro, aspart) are comparable in safety and superior in glucose control to regular human insulin. Because the safety of long-acting insulin analogs (glargine, detemir) in pregnancy has not firmly established, the use of human insulin is preferred over basal insulin. Among the oral hypoglycemic agents, metformin and glyburide might be considered as alternative therapies.
Abortion, Spontaneous ; Administration, Oral ; Complementary Therapies ; Diabetes, Gestational ; Female ; Glucose ; Glyburide ; Humans ; Hypoglycemic Agents ; Insulin ; Insulin, Long-Acting ; Insulin, Short-Acting ; Life Style ; Metformin ; Perinatal Mortality ; Pregnancy ; Pregnant Women ; Premature Birth ; Resin Cements

Diabetic heart disease is a growing and important public health risk. Apart from the risk of coronary artery disease or hypertension, diabetes mellitus (DM) is a well-known risk factor for heart failure in the form of diabetic cardiomyopathy (DiaCM). Currently, DiaCM is defined as myocardial dysfunction in patients with DM in the absence of coronary artery disease and hypertension. The underlying pathomechanism of DiaCM is partially understood, but accumulating evidence suggests that metabolic derangements, oxidative stress, increased myocardial fibrosis and hypertrophy, inflammation, enhanced apoptosis, impaired intracellular calcium handling, activation of the renin-angiotensin-aldosterone system, mitochondrial dysfunction, and dysregulation of microRNAs, among other factors, are involved. Numerous animal models have been used to investigate the pathomechanisms of DiaCM. Despite some limitations, animal models for DiaCM have greatly advanced our understanding of pathomechanisms and have helped in the development of successful disease management strategies. In this review, we summarize the current pathomechanisms of DiaCM and provide animal models for DiaCM according to its pathomechanisms, which may contribute to broadening our understanding of the underlying mechanisms and facilitating the identification of possible new therapeutic targets.

BACKGROUND: The risk of developing diabetes is high in the offspring of patients with type 2 diabetes. There have been no studies to assess the offspring's awareness of the risk of developing diabetes. The aim of this study was to investigate how the male offspring of type 2 diabetic patients assess their likelihood of developing diabetes. METHODS: One hundred and one non-diabetic men with one or both parents having type 2 diabetes, aged 19-28 years, were recruited. RESULTS: Thirty-nine subjects (38.6%) were concerned about diabetes and 85 (84.2%) considered diabetes a serious problem. However, only 10 (9.9%) thought they might develop diabetes and 9 (8.9%) had previously attended diabetes education programs with their parents. The educational level amongst the diabetic parents was the only independent predictor of perception of the increased risk. Age, body mass index, waist-to-hip ratio, educational level and the perception of diabetes as a serious problem were not associated with perception of the increased risk. CONCLUSION: Most offspring of diabetic parents lacked knowledge about the increased risk amongst family members. We suggest that physicians and diabetic educators should provide knowledge about the increased risk of developing diabetes in offspring and the benefit of lifestyle modification to delay or prevent the development of the disease.
Adult ; Body Mass Index ; Diabetes Mellitus, Non-Insulin-Dependent/epidemiology/*genetics ; Educational Status ; Family ; Human ; *Knowledge, Attitudes, Practice ; Korea ; Logistic Models ; Male ; Military Personnel ; Questionnaires ; Risk Factors

One of the histopathologic hallmarks of early diabetic retinopathy is the loss of pericytes. Evidences suggest that the pericyte loss in vivo is mediated by apoptosis. However, the underlying cause of pericyte apoptosis is not fully understood. This study investigated the influence of methylglyoxal (MGO), a reactive -dicarbonyl compound of glucose metabolism, on apoptotic cell death in bovine retinal pericytes. Analysis of internucleosomal DNA fragmentation by ELISA showed that MGO (200 to 800 micrometer) induced apoptosis in a concentration-dependent manner. Intracellular reactive oxygen species were generated earlier and the antioxidant, N-acetyl cysteine, inhibited the MGO-induced apoptosis. NF-kB activation and increased caspase- 3 activity were detected. Apoptosis was also inhibited by the caspase-3 inhibitor, Z-DEVD-fmk, or the NF- kB inhibitor, pyrrolidine dithiocarbamate. These data suggest that elevated MGO levels observed in diabetes may cause apoptosis in bovine retinal pericytes through an oxidative stress mechanism and suggests that the nuclear activation of NF-kB are involved in the apoptotic process.
Acetylcysteine/pharmacology ; Animals ; *Apoptosis ; Caspases/metabolism ; Cattle ; Cell Death ; Cell Survival ; DNA Fragmentation ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Glucose/metabolism ; NF-kappa B/metabolism ; Nucleosomes/metabolism ; Oxidative Stress ; Pericytes/*drug effects ; Pyruvaldehyde/*pharmacology ; *Reactive Oxygen Species ; Retina/cytology/*drug effects