The Influence of Baseline Diastolic Blood Pressure on the Effects of Intensive Blood Pressure Lowering on Cardiovascular Outcomes and All-Cause Mortality in Type 2 Diabetes.

Objective: To examine whether low baseline diastolic blood pressure (DBP) modifies the effects of intensive systolic blood pressure (SBP) lowering on cardiovascular outcomes in type 2 diabetes mellitus (T2DM).

Research Design And Methods: The Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP), a two-by-two factorial randomized controlled trial, examined effects of SBP (<120 vs. <140 mmHg) and glycemic (HbA <6% vs.

Identification of a Paracrine Signaling Mechanism Linking CD34 Progenitors to the Regulation of Visceral Fat Expansion and Remodeling.

Accumulation of visceral (VIS) is a predictor of metabolic disorders and insulin resistance. This is due in part to the limited capacity of VIS fat to buffer lipids allowing them to deposit in insulin-sensitive tissues. Mechanisms underlying selective hypertrophic growth and tissue remodeling properties of VIS fat are not well understood.

Antioxidant treatment normalizes mitochondrial energetics and myocardial insulin sensitivity independently of changes in systemic metabolic homeostasis in a mouse model of the metabolic syndrome.

Cardiac dysfunction in obesity is associated with mitochondrial dysfunction, oxidative stress and altered insulin sensitivity. Whether oxidative stress directly contributes to myocardial insulin resistance remains to be determined. This study tested the hypothesis that ROS scavenging will improve mitochondrial function and insulin sensitivity in the hearts of rodent models with varying degrees of insulin resistance and hyperglycemia.

Treatment with a SOD mimetic reduces visceral adiposity, adipocyte death, and adipose tissue inflammation in high fat-fed mice.

Objective: Obesity is associated with enhanced reactive oxygen species (ROS) accumulation in adipose tissue. However, a causal role for ROS in adipose tissue expansion after high fat feeding is not established. The aim of this study is to investigate the effect of the cell permeable superoxide dismutase mimetic and peroxynitrite scavenger Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP) on adipose tissue expansion and remodeling in response to high fat diet (HFD) in mice.

Mechanistic target of rapamycin (Mtor) is essential for murine embryonic heart development and growth.

Mechanistic target of rapamycin (Mtor) is required for embryonic inner cell mass proliferation during early development. However, Mtor expression levels are very low in the mouse heart during embryogenesis. To determine if Mtor plays a role during mouse cardiac development, cardiomyocyte specific Mtor deletion was achieved using α myosin heavy chain (α-MHC) driven Cre recombinase.

Cardiac dysfunction and oxidative stress in the metabolic syndrome: an update on antioxidant therapies.

The metabolic syndrome (MetS) is a cluster of risk factors including obesity, insulin resistance, dyslipidemia, elevated blood pressure and glucose intolerance. The MetS increases the risk for cardiovascular disease (CVD) and type 2 diabetes. Each component of the MetS causes cardiac dysfunction and their combination carries additional risk.

Cardiac PI3K-Akt impairs insulin-stimulated glucose uptake independent of mTORC1 and GLUT4 translocation.

Impaired insulin-mediated glucose uptake characterizes cardiac muscle in humans and animals with insulin resistance and diabetes, despite preserved or enhanced phosphatidylinositol 3-kinase (PI3K) and the serine-threonine kinase, Akt-signaling, via mechanisms that are incompletely understood. One potential mechanism is PI3K- and Akt-mediated activation of mechanistic target of rapamycin (mTOR) and ribosomal protein S6 kinase (S6K), which may impair insulin-mediated activation of insulin receptor substrate (IRS)1/2 via inhibitory serine phosphorylation or proteasomal degradation. To gain mechanistic insights by which constitutive activation of PI3K or Akt may desensitize insulin-mediated glucose uptake in cardiomyocytes, we examined mice with cardiomyocyte-restricted, constitutive or inducible overexpression of a constitutively activated PI3K or a myristoylated Akt1 (myrAkt1) transgene that also expressed a myc-epitope-tagged glucose transporter type 4 protein (GLUT4).

Modulation of glucose transporter 1 (GLUT1) expression levels alters mouse mammary tumor cell growth in vitro and in vivo.

Tumor cells exhibit an altered metabolism characterized by elevated aerobic glycolysis and lactate secretion which is supported by an increase in glucose transport and consumption. We hypothesized that reducing or eliminating the expression of the most prominently expressed glucose transporter(s) would decrease the amount of glucose available to breast cancer cells thereby decreasing their metabolic capacity and proliferative potential.Of the 12 GLUT family glucose transporters expressed in mice, GLUT1 was the most abundantly expressed at the RNA level in the mouse mammary tumors from MMTV-c-ErbB2 mice and cell lines examined.

Contribution of impaired myocardial insulin signaling to mitochondrial dysfunction and oxidative stress in the heart.

Background: Diabetes-associated cardiac dysfunction is associated with mitochondrial dysfunction and oxidative stress, which may contribute to left ventricular dysfunction. The contribution of altered myocardial insulin action, independent of associated changes in systemic metabolism, is incompletely understood. The present study tested the hypothesis that perinatal loss of insulin signaling in the heart impairs mitochondrial function.

Mechanisms for increased myocardial fatty acid utilization following short-term high-fat feeding.

Aims: Diet-induced obesity is associated with increased myocardial fatty acid (FA) utilization, insulin resistance, and cardiac dysfunction. The study was designed to test the hypothesis that impaired glucose utilization accounts for initial changes in FA metabolism.

Methods And Results: Ten-week-old C57BL6J mice were fed a high-fat diet (HFD, 45% calories from fat) or normal chow (4% calories from fat).

Benz(2-heteroaryl)cyanoximes and their Tl(i) complexes: new room temperature blue emitters.

A series of five 2-heteroarylcyanoximes such as: alpha-oximino-(2-benzimidazolyl)acetonitrile (HBIHCO), alpha-oximino-(N-methy-l-2-benzimidazolyl)acetonitrile (HBIMCO), alpha-oximino-(2-benzoxazolyl)acetonitrile (HBOCO), alpha-oximino-(2-benzothiazolyl)acetonitrile (HBTCO) and alpha-oximino-(2-quinolyl)acetonitrile (HQCO) and their monovalent thallium(i) complexes were synthesized and characterized using spectroscopic methods ((1)H, (13)C NMR, IR, UV-visible, mass-spectrometry) and X-ray analysis. The HBIMCO (as monohydrate) adopts planar trans-anti configuration in the solid state. The crystal structure of "HBOCO" revealed the presence of nitroso anion a, BOCO(-), and protonated oxime cation b, H(2)BOCO(+), that form a H-bonded dimer in the unit cell.

DNA binding affinity and sequence permutation preference of the telomere protein from Euplotes crassus.

Telomere end binding proteins from diverse organisms use various forms of an ancient protein structure to recognize and bind with single-strand DNA found at the ends of telomeres. To further understand the biochemistry and evolution of these proteins, we have characterized the DNA binding properties of the telomere end binding protein from Euplotes crassus (EcTEBP). EcTEBP and its predicted amino-terminal DNA-binding domain, EcTEBP-N, were expressed in Escherichia coli and purified.