[Effect of Statins on Glycemic Status and Plasma Adiponectin Concentrations in Patients with Type 2 Diabetes Mellitus and Hypercholesterolemia].

It is reported that statins have inconsistent effects on glycemic status and adiponectin concentrations in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the effect of statins on these variables in patients with T2DM and hypercholesterolemia. A control group comprising 24 patients with T2DM but without hypercholesterolemia was observed for more than 12 weeks, while 24 patients with T2DM and hypercholesterolemia were treated with statins for the same period (statin group).

Epidermal growth factor receptor transactivation is necessary for glucagon-like peptide-1 to protect PC12 cells from apoptosis.

Aim: Patients with long-standing diabetes commonly develop diabetic encephalopathy, which is characterized by cognitive impairment and dementia. To identify potential treatments for diabetic encephalopathy, we focused on the protective action of glucagon-like peptide-1 (GLP-1) against neural cell apoptosis. In this study, we evaluated whether exposure of cells to GLP-1 leads to epidermal growth factor receptor (EGFR) transactivation and signaling through the PI3K/Akt/mTOR/GCLc/redox pathway, which we previously reported.

Preservation of cellular glutathione status and mitochondrial membrane potential by N-acetylcysteine and insulin sensitizers prevent carbonyl stress-induced human brain endothelial cell apoptosis.

Oxidative stress-induced cerebral endothelial cell dysfunction is associated with cerebral microvascular complication of primary diabetic encephaolopathy, a neurodegenerative disorder of long-standing diabetes, but the injury mechanisms are poorly understood. This study sought to determine the contribution of carbonyl (methylglyoxal, MG) stress to human brain endothelial cell (IHEC) apoptosis, the relationship to cellular redox status and mitochondrial membrane potential, and the protection by thiol antioxidant and insulin sensitizers. MG exposure induced IHEC apoptosis in association with perturbed cellular glutathione (GSH) redox status, decreased mitochondrial membrane potential (Deltapsi(m)), activation of caspase-9 and -3, and cleavage of polyADP-ribose polymerase.

Alteration of the responses of gastric smooth muscle to endothelin in streptozotocin-induced diabetic rats.

Diabetic gastropathy is suggested to be the result of not only an autonomic neuropathy but also to disorder of the spontaneous rhythmic motility of the gastric smooth muscle. Attempts were made to investigate the alteration of the effects of endothelin-1 (ET-1), which is known to enhance the spontaneous activity of gastrointestinal smooth muscle, on gastric activity in streptozotocin (STZ)-induced diabetic rats. STZ-induced diabetic rats were prepared by the injection of Sprague-Dawley (SD) rats with STZ (i.

Severe ascites with hypothyroidism and elevated CA125 concentration: a case report.

Ascites caused by hypothyroidism is rare and the pathogenesis is unclear. Several reports have presented cases of progressive ascites with hypothyroidism and elevated tumor markers. We report a 31-year-old female case with massive ascites and elevated serum CA 125 concentrations.

Effects of histamine 2 receptor antagonists on endothelial-neutrophil adhesion and surface expression of endothelial adhesion molecules induced by high glucose levels.

Neutrophil-endothelial adhesion is a crucial step in vascular inflammation and is recognized as a direct cause of serious atherosclerosis-mediated diseases. We previously demonstrated that high concentrations of glucose increased adhesion in a protein kinase C (PKC)-dependent manner within 48 h of administration by increasing the surface expression of endothelial adhesion molecules. In this study, we focused on the effects of histamine 2 receptor antagonists on endothelial-neutrophil adhesion and on the surface expression of endothelial adhesion molecules mediated by high glucose levels.

NRF2-dependent glutamate-L-cysteine ligase catalytic subunit expression mediates insulin protection against hyperglycemia- induced brain endothelial cell apoptosis.

Increased oxidative stress and susceptibility of brain endothelium are contributing factors in the development of central nervous system complications in neuro-degenerative disorders in diabetes, Alzheimer's and Parkinson's disease. The molecular mechanisms underpinning the vulnerability of brain endothelial cells to chronic oxidative challenge have not been elucidated. Here, we investigated the oxidative susceptibility of human brain endothelial cells (IHEC) to chronic hyperglycemic stress and insulin signaling and cytoprotection.

Hyperglycemia potentiates carbonyl stress-induced apoptosis in naïve PC-12 cells: relationship to cellular redox and activator protease factor-1 expression.

The mechanism(s) of central nervous system complication associated with neurodegenerative disorders such as diabetes is unknown. Previous studies demonstrated that carbonyl stress induced by methylglyoxal (MG) mediates differential apoptosis of rat pheochromocytoma (PC12) cells in the naïve or differentiated transition states. Since chronic hyperglycemia is central to diabetic complications, and poorly differentiated cells are oxidatively more vulnerable, we currently investigated the effect of glycemic status on MG-induced apoptosis in naïve (nPC12) cells focusing on glutathione-to-glutathione disulfide (GSH/GSSG) redox signaling.

Differential susceptibility of naive and differentiated PC-12 cells to methylglyoxal-induced apoptosis: influence of cellular redox.

Neuropathologies have been associated with neuronal de-differentiation and oxidative susceptibility. To address whether cellular states determines their oxidative vulnerability, we have challenged naive (undifferentiated) and nerve growth factor-induced differentiated pheochromocytoma (PC12) with methylglyoxal (MG), a model of carbonyl stress. MG dose-dependently induced greater apoptosis (24 h) in naive (nPC12) than differentiated (dPC12) cells.

Insulin enhances leukocyte-endothelial cell adhesion in the retinal microcirculation through surface expression of intercellular adhesion molecule-1.

The purpose of this study was to evaluate the effects of insulin on leukocyte-endothelial cell adhesion in the retinal microcirculation in vitro and in vivo. Human retinal endothelial cells (HRECs) were cultured in medium with or without insulin, and neutrophils allowed to adhere. Adherent neutrophils were quantified by measuring myeloperoxidase activity.

Effects of endothelin-1 on the membrane potential and slow waves in circular smooth muscle of rat gastric antrum.

Electrophysiological effects of endothelin-1 (ET-1) on circular smooth muscle of rat gastric antrum were investigated by using intracellular membrane potential recording techniques. ET-1 (10 nM) caused an initial hyperpolarization of the membrane which was followed by a sustained depolarization. ET-1 also increased the frequency but not the amplitude of slow waves.

Effects of insulin on the acetylcholine-induced hyperpolarization in the guinea pig mesenteric arterioles.

Background: Insulin induces endothelium-dependent vasodilatation, which may be casually related to the insulin resistance and hypertension. Endothelium-derived nitric oxide (NO) is the most important mechanism of insulin-induced vasodilatation, and a possible contribution of endothelium-derived hyperpolarizing factor (EDHF) is also considered. Attempts were made to observe the effects of insulin on acetylcholine (ACh)-induced hyperpolarization in the submucosal arteriole of the guinea pig ileum, the objective being to investigate possible involvement of EDHF in the actions of insulin.

Cilostazol inhibits high glucose-mediated endothelial-neutrophil adhesion by decreasing adhesion molecule expression via NO production.

Objective: Endothelial-neutrophil adhesion is crucial for vascular injury, the major cause of diabetic vascular complications. On the other hand, platelet aggregation inhibitors, frequently used for diabetic patients with intermittent claudication, have been shown to decrease the incidence of atherosclerosis-mediated diseases (acute myocardial infarction and stroke). However, whether these agents act directly on the endothelial reactions to hyperglycemia remains unclear.

The antidiabetic agent, gliclazide, reduces high insulin-enhanced neutrophil-transendothelial migration through direct effects on the endothelium.

Background And Aim: Many lines of evidence indicate that hyperinsulinemia might be associated with coronary atherosclerosis, and, currently, there are no effective strategies for preventing this. We previously reported that high insulin enhances neutrophil-transendothelial migration, a process that involves increased surface presentation of platelet endothelial cell adhesion molecule-1 (PECAM-1) through a mitogen-activated protein (MAP) kinase-dependent event. In this current study, we examined if antidiabetic agents, especially K(ATP) channel blockers, might similarly protect against the leukocyte-endothelial cell interactions enhanced by high insulin.

Noninvasive detection of coronary artery bypass graft patency by intravenous electron beam computed tomographic angiography.

This study evaluates the usefullness of intravenous electron beam computed tomographic angiography (EBA) for the detection of coronary artery bypass graft patency in 43 patients (33 men and 10 women, mean age, 65 years) who had coronary artery bypass graft surgery. EBA was performed a few days before selective bypass graft angiography (SGA). Forty axial cross-sections of angiographic images of the heart were acquired consecutively by an electrocardiographic trigger signal at 40% of the RR interval, which corresponds to the end-systolic phase.

Protective actions of gliclazide on high insulin-enhanced neutrophil-endothelial cell interactions through inhibition of mitogen activated protein kinase and protein kinase C pathways.

Background And Aim: There are many lines of evidence indicating that hyperinsulinemia but not hyperglycemia is linked to the development of atherosclerotic diseases such as coronary events in diabetic patients. K(ATP) channel blockers of the sulphonylurea class are used widely to treat type 2 diabetes mellitus even with hyperinsulinemia. In this study, we determined whether K(ATP) channel blockers can protect against atherosclerotic processes enhanced by hyperinsulinemia, namely leukocyte-endothelial cell interactions.

Cerivastatin ameliorates high insulin-enhanced neutrophil-endothelial cell adhesion and endothelial intercellular adhesion molecule-1 expression by inhibiting mitogen-activated protein kinase activation.

Background And Aims: There is growing evidence that hyperinsulinemia is linked to the development of atherosclerosis in patients with diabetes. We demonstrated previously that high insulin exacerbates neutrophil-endothelial cell adhesion and endothelial intercellular adhesion molecule (ICAM)-1 expression through activation of protein kinase C (PKC) and mitogen-activated protein (MAP) kinase. Though 3-hydroxymethyl-3-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been employed as therapeutic agents in the treatment of dyslipidemia, which is frequently accompanied by diabetes mellitus; it is not known whether statins protect against leukocyte-endothelial interactions, especially in hyperinsulinemia.

Statins inhibit high glucose-mediated neutrophil-endothelial cell adhesion through decreasing surface expression of endothelial adhesion molecules by stimulating production of endothelial nitric oxide.

Neutrophil-endothelial adhesion is a crucial step in vascular inflammation, which is recognized as the direct cause of atherosclerosis-mediated serious diseases. We demonstrated previously that high glucose increased adhesion in a protein kinase C (PKC)-dependent manner within 48 h through increasing surface expression of endothelial adhesion molecules. On the other hand, statins, used for patients with hypercholesterolemia, have been shown to decrease the incidence of atherosclerosis-mediated diseases, but direct effects of statins on endothelial cells remain unclear.

Increased intracellular calcium activates serum and glucocorticoid-inducible kinase 1 (SGK1) through a calmodulin-calcium calmodulin dependent kinase kinase pathway in Chinese hamster ovary cells.

SGK1 is one of the protein-serine/threonine kinases that is activated by insulin in a PI3K-dependent manner. Although SGK1 mediates a variety of biological activities, the mechanisms regulating its activity remain unclear. In this study, we examined the potential roles of calcium signaling in the activation of SGK1.

The mechanisms of inhibitory actions of gliclazide on neutrophils-endothelial cells adhesion and surface expression of endothelial adhesion molecules mediated by a high glucose concentration.

Background: We previously reported that culture of endothelial cells in the presence of high glucose concentrations (27.8 and 55.5 mM) increase neutrophils adhesion because of the increase in endothelial adhesion molecules expression via activation of a protein kinase C (PKC) pathway.

Protective actions of rat gastric epithelial E-cadherin expression against epithelial barrier dysfunctions induced by chemical hypoxia-reoxygenation in vitro.

Background And Aim: E-cadherin expressed on gastric epithelium is reported to form adherence junctions and stabilize barrier functions. While hypoxia-reoxygenation is well known to cause gastric mucosal injury during reoxygenation, gastric E-cadherin actions against this stress remain unclear. In this study, using the oxygen depleting agent thioglycolic acid we examined whether E-cadherin expressed on rat cultured gastric epithelial cells has protective actions against epithelial barrier dysfunction induced by chemical hypoxia-reoxygenation.

Mechanisms of inhibitory activity of the aldose reductase inhibitor, epalrestat, on high glucose-mediated endothelial injury: neutrophil-endothelial cell adhesion and surface expression of endothelial adhesion molecules.

Background: We have previously reported that endothelial cells cultured in the presence of high concentrations of glucose (27.8 and 55.5 mM) exhibited enhanced neutrophil adhesion through increased expression of endothelial adhesion molecules via the activation of a protein kinase C (PKC)-dependent pathway.

Identification of an occludin cell adhesion recognition sequence.

The molecular mechanisms by which the tight junction integral membrane protein, occludin promotes cell adhesion and establishes an endothelial monolayer permeability barrier have not been elucidated. In particular, the amino acid sequences of the occludin cell adhesion recognition (CAR) sites have not been determined. Here we demonstrate that a cyclic peptide containing the sequence LYHY, which is found in the second extracellular domain of occludins in all mammalian species, inhibits the establishment of endothelial cell barriers in vitro and in vivo.

Participation of high glucose concentrations in neutrophil adhesion and surface expression of adhesion molecules on cultured human endothelial cells: effect of antidiabetic medicines.

Background: Atherosclerosis and vascular inflammation induced by hyperglycemia are important factors in the promotion of diabetic complications. One of the earliest events in the inflammatory process is increased binding of neutrophils to endothelial cells. Since vascular inflammation has been recently reported to be crucial for the onset of atherosclerosis-mediated serious diseases (acute myocardial infarction, stroke), in this study, we examined the effects of high glucose concentrations on endothelial-neutrophil cell adhesion and surface expression of endothelial adhesion molecules.