A Hemilabile NHC-Gold Complex and its Application to the Redox Neutral 1,2-Oxyarylation of Feedstock Alkenes.

We describe a Au complex of a hemi-labile (C^N) N-heterocyclic carbene ligand that is able to mediate oxidative addition of aryl iodides. Detailed computational and experimental investigations have been undertaken to verify and rationalize the oxidative addition process. Application of this initiation mode has resulted in the first examples of "exogenous oxidant-free" Au /Au catalyzed 1,2-oxyarylations of ethylene and propylene.

'Reverse biomimetic' synthesis of l-arogenate and its stabilized analogues from l-tyrosine.

l-Arogenate (also known as l-pretyrosine) is a primary metabolite on a branch of the shikimate biosynthetic pathway to aromatic amino acids. It plays a key role in the synthesis of plant secondary metabolites including alkaloids and the phenylpropanoids that are the key to carbon fixation. Yet understanding the control of arogenate metabolism has been hampered by its extreme instability and the lack of a versatile synthetic route to arogenate and its analogues.

DNA barcoding fishes from the Congo and the Lower Guinean provinces: Assembling a reference library for poorly inventoried fauna.

The Congolese and Lower Guinean ichthyological provinces are understudied hotspots of the global fish diversity. Here, we barcoded 741 specimens from the Lower and Middle Congo River and from three major drainage basins of the Lower Guinean ichthyological province, Kouilou-Niari, Nyanga and Ogowe. We identified 194 morphospecies belonging to 82 genera and 25 families.

Duodenal GLP-1 signaling regulates hepatic glucose production through a PKC-δ-dependent neurocircuitry.

Intestinal glucagon-like peptide-1 (GLP-1) is a hormone that stimulates insulin secretion and acts as a neuropeptide to control glucose homeostasis, but little is known whether intestinal GLP-1 has any effect in the control of hepatic glucose production (HGP). Here we found that intraduodenal infusion of GLP-1 activated duodenal PKC-δ, lowered HGP and was accompanied by a decrease in hepatic expression of gluconeogenic enzymes and an increase in hepatic insulin signaling in rats. However, gut co-infusion of either the GLP-1 receptor antagonist Ex-9, or the PKC-δ inhibitor rottlerin with GLP-1, negated the ability of gut GLP-1 to lower HGP and to increase hepatic insulin signaling during clamps.

NAMPT knockdown attenuates atherosclerosis and promotes reverse cholesterol transport in ApoE KO mice with high-fat-induced insulin resistance.

NAMPT has been suggested association with atherosclerosis and insulin resistance. However, the impact of NAMPT on atherosclerosis remained unknown. Therefore, the objective of this study was to use a NAMPT loss-of-function approach to investigate the effect of NAMPT on atherosclerosis in hypercholesterolemic mice.

Central administration of vaspin inhibits glucose production and augments hepatic insulin signaling in high-fat-diet-fed rat.

Objective: To investigate the effects of vaspin signaling conveyed by the brain on liver glucose fluxes in rats.

Methods: To determine the effects and underlying mechanisms of central vaspin signaling, normal-chow-diet- and high-fat-diet (HFD)-fed rats with or without hepatic branch vagotomy (HBV) received acute infusion of vaspin to the third cerebral ventricle or MK801, a dorsal vagal complex (DVC) N-methyl-D-aspartate (NMDA) receptor inhibitor, to the DVC during the pancreatic euglycemic clamp.

Results: Central administration of vaspin in HFD-fed rats significantly increased glucose infusion required to maintain euglycemia owing to an inhibition of glucose production during the clamps.

Excessive caloric intake acutely causes oxidative stress, GLUT4 carbonylation, and insulin resistance in healthy men.

Obesity-linked insulin resistance greatly increases the risk for type 2 diabetes, hypertension, dyslipidemia, and non-alcoholic fatty liver disease, together known as the metabolic or insulin resistance syndrome. How obesity promotes insulin resistance remains incompletely understood. Plasma concentrations of free fatty acids and proinflammatory cytokines, endoplasmic reticulum ( ER) stress, and oxidative stress are all elevated in obesity and have been shown to induce insulin resistance.

Stressful life events are associated with insulin resistance among Chinese immigrant women in the United States.

Background: Chinese immigrants experience increased chronic disease risk following migration to the US. Although the impact of lifestyle changes (e.g.

Tissue factor and Toll-like receptor (TLR)4 in hyperglycaemia-hyperinsulinaemia. Effects in healthy subjects, and type 1 and type 2 diabetes mellitus.

Diabetes mellitus (DM) patients have an increased incidence of cardiovascular events. Blood tissue factor-procoagulant activity (TF-PCA), the initiating mechanism for blood coagulation, is elevated in DM. We have shown that hyperglycaemia (HG), hyperinsulinaemia (HI) and combined HG+HI (induced using 24-hour infusion clamps) increases TF-PCA in healthy and type 2 DM (T2DM) subjects, but not in type 1 DM (T1DM) subjects.

Transcription factor TIP27 regulates glucose homeostasis and insulin sensitivity in a PI3-kinase/Akt-dependent manner in mice.

Background/objectives: Juxtaposed with another zinc-finger gene 1 (TIP27 or JAZF1) is a 27-kDa transcription factor, and genome-wide association studies have recently revealed TIP27 to be associated with type 2 diabetes. However, little is known about its role in the regulation of metabolism. In this study, we investigated the effects of TIP27 overexpression on glucose homeostasis and insulin signaling in high-fat diet (HFD)-fed TIP27 transgenic (TIP27-Tg) mice and db/db mice.

Effect of dietary fat and food consistency on gastroparesis symptoms in patients with gastroparesis.

Background: Nutrition therapy for gastroparesis focuses on reducing meal size, fiber, fat intake, and increasing liquids intake relative to solid foods. Evidence to support these dietary interventions has been anecdotal. The aim of this study was to determine the effect of fat intake and solid/liquid meal consistency on symptoms in gastroparesis.

Overexpression of JAZF1 protected ApoE-deficient mice from atherosclerosis by inhibiting hepatic cholesterol synthesis via CREB-dependent mechanisms.

Genome wide association studies have suggested an association of Juxtaposed with another zinc finger gene 1(JAZF1) with type 2 diabetes mellitus (T2DM). As an inhibitor of the TAK1/TR4 signaling pathway, JAZF1 has been shown to be involved in gluconeogenesis, lipid metabolism and insulin sensitivity. However, its role in insulin resistance and atherosclerosis in vivo remains unknown.

Development and validation of a parent-report measure for detection of cognitive delay in infancy.

Aim: To develop a brief, parent-completed instrument (ERIC - Early Report by Infant Caregivers) for detection of cognitive delay in 10- to 24-month-olds born preterm, or of low birthweight, or with perinatal complications, and to establish ERIC's diagnostic properties.

Method: Scores for ERIC were collected from the parents of 317 children meeting ≥inclusion criterion (birthweight <1500 g, gestational age <34 completed weeks, 5 min Apgar score <7, or presence of hypoxic-ischaemic encephalopathy) and no exclusion criteria. Children were assessed using a criterion score of below 80 on the Bayley Scales of Infant and Toddler Development-III cognitive scale.

Alterations in insulin-signaling and coagulation pathways in platelets during hyperglycemia-hyperinsulinemia in healthy non-diabetic subject.

Introduction: Diabetes mellitus (DM) is a prothrombotic and proinflammatory state. Hyperglycemia (HG) is encountered even in patients without DM. We have shown that combined HG and hyperinsulinemia (HI) in healthy non-diabetic subjects increased circulating tissue factor (TF) and thrombin generation.

Insulin resistance is associated with diminished endoplasmic reticulum stress responses in adipose tissue of healthy and diabetic subjects.

We recently showed that insulin increased ER stress in human adipose tissue. The effect of insulin resistance on ER stress is not known. It could be decreased, unchanged, or increased, depending on whether insulin regulates ER stress via the metabolic/phosphoinositide 3-kinase (PI3K) or alternate signaling pathways.

Silencing of FGF-21 expression promotes hepatic gluconeogenesis and glycogenolysis by regulation of the STAT3-SOCS3 signal.

Insulin resistance is a metabolic disorder associated with type 2 diabetes. Recent reports have shown that fibroblast growth factor-21 (FGF-21) plays an important role in the progression of insulin resistance. However, the biochemical and molecular mechanisms by which changes in FGF-21 activation result in changes in the rates of hepatic gluconeogenesis and glycogenolysis remain to be elucidated.

Efficacy and safety of aldose reductase inhibitor for the treatment of diabetic cardiovascular autonomic neuropathy: systematic review and meta-analysis.

Background: Aldose reductase inhibitors (ARIs) can block the metabolism of the polyol pathway, and have been used to slow or reverse the progression of diabetic cardiovascular autonomic neuropathy (DCAN). The purpose of this study was to review the effectiveness and safety of ARIs in the treatment of DCAN as determined by five cardiac autonomic neuropathy function tests.

Methods: CENTRAL, MEDLINE, EMBASE, Scopus databases (inception to May 2012) were searched to identify randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs) investigating ARIs for the treatment of DCAN with an English-language restriction.

Hypothalamic nesfatin-1/NUCB2 knockdown augments hepatic gluconeogenesis that is correlated with inhibition of mTOR-STAT3 signaling pathway in rats.

Nesfatin-1, an 82-amino acid neuropeptide, has recently been characterized as a potent metabolic regulator. However, the metabolic mechanisms and signaling steps directly associated with the action of nesfatin-1 have not been well delineated. We established a loss-of-function model of hypothalamic nesfatin-1/NUCB2 signaling in rats through an adenoviral-mediated RNA interference.

Bodyweight in patients with idiopathic gastroparesis: roles of symptoms, caloric intake, physical activity, and body metabolism.

Background: Most gastroparetic patients are underweight probably because of frequently experienced early satiety, nausea, and vomiting. Some gastroparesis (GP) patients, however, are overweight, for reasons that are not well understood. The aim of this study was to evaluate the factors that influence bodyweight such as resting energy and exercise-related expenditure, symptoms of early satiety, nausea and vomiting, and caloric intake in patients with idiopathic GP and in healthy controls.

Changes in insulin sensitivity and insulin secretion with the sodium glucose cotransporter 2 inhibitor dapagliflozin.

Aim: This randomized, double-blind, placebo-controlled parallel-group study assessed the effects of sodium glucose cotransporter 2 inhibition by dapagliflozin on insulin sensitivity and secretion in subjects with type 2 diabetes mellitus (T2DM), who had inadequate glycemic control with metformin (with or without an insulin secretagogue).

Subjects And Methods: Forty-four subjects were randomized to receive dapagliflozin 5 mg or matching placebo once daily for 12 weeks. Subjects continued stable doses of background antidiabetes medication throughout the study.

Insulin regulates the unfolded protein response in human adipose tissue.

Endoplasmic reticulum (ER) stress is increased in obesity and is postulated to be a major contributor to many obesity-related pathologies. Little is known about what causes ER stress in obese people. Here, we show that insulin upregulated the unfolded protein response (UPR), an adaptive reaction to ER stress, in vitro in 3T3-L1 adipocytes and in vivo, in subcutaneous (sc) adipose tissue of nondiabetic subjects, where it increased the UPR dose dependently over the entire physiologic insulin range (from ∼ 35 to ∼ 1,450 pmol/L).

Comparison of in vivo effects of insulin on SREBP-1c activation and INSIG-1/2 in rat liver and human and rat adipose tissue.

Objective: The stimulatory effects of insulin on de novo lipogenesis (DNL) in the liver, where it is an important contributor to non-alcoholic fatty liver disease (NAFLD), hepatic and systemic insulin resistance, is strong and well established. In contrast, insulin plays only a minor role in DNL in adipose tissue. The reason why insulin stimulates DNL more in liver than in fat is not known but may be due to differential regulation of the transcription and post-translational activation of sterol regulatory element binding proteins (SREBPs).

A Single A1C >= 6.5% Accurately Identifies Type 2 Diabetes/Impaired Glucose Tolerance in African Americans.

Objective: In 2010, the American Diabetes Association revised its criteria for the diagnosis of diabetes to include A1C ≥ 6.5%; however, this has remained controversial, particularly for African Americans. The objective of this pilot study was to examine the usefulness of a single A1C determination in comparison with a same day 2-hour oral glucose tolerance test to diagnose type 2 diabetes in African Americans.

Why does obesity increase the risk for cardiovascular disease?

Insulin resistance and inflammation are recognized as important links between obesity and cardiovascular disease (CVD). Plasma free fatty acids (FFA), either released from the abnormally enlarged adipose tissue or as part of the excessive nutrient intake, produce insulin resistance and inflammation. Both insulin resistance and inflammation are tightly linked to several independent CVD risk factors such as type 2 diabetes (T2DM), hypertension, dyslipidemia and disorders of blood coagulation.