Berberine, a major isoquinoline alkaloid present in Chinese herb Rhizoma coptidis, is a potent inhibitor of inflammation and has anti-diabetic activity. This study aims to investigate effects of berberine on ameliorating insulin resistance and molecular mechanisms involved in HepG2 cells. Inflammatory responses and insulin resistance were induced by palmitate (PA) ...

BACKGROUND: Type 2 diabetes mellitus is highly prevalent in obese individuals. Bariatric surgery, promoted for reducing the medical problems of morbid obesity, has been increasingly recognized for its particular efficacy in treating diabetes. However, before bariatric surgery can be recommended for the treatment of diabetes, its safety in the diabetic ...

Introduction.  It has been suggested that the up-regulation of the contractile RhoA/Rho-kinase (ROCK) signaling pathway is one of the important mechanisms for diabetes-associated erectile dysfunction (ED). However, the exact role of RhoA/ROCK signaling in the pathogenesis of diabetes-related ED has not been fully delineated. Aim.  To determine whether the RhoA/ROCK ...

After isolating NT-S100A8 from pancreatic cancer (PC) tissue of diabetic patients, we verified whether this peptide alters PC cell growth and invasion and/or insulin release and [Ca(2+)](i) oscillations of insulin secreting cells and/or insulin signaling. BxPC3, Capan1, MiaPaCa2, Panc1 (PC cell lines) cell growth, and invasion were assessed in the ...

Diabetes is a profound disease that results in a severe lack of regulation of systemic salt and water balance. From our earlier work on the endocrine regulation of salt taste at the level of the epithelial sodium channel (ENaC), we have begun to investigate the ability of insulin to alter ...

Obesity, the metabolic syndrome, and aging share several pathogenic features in both humans and non-human primates, including insulin resistance and inflammation. Since muscle and liver are considered key integrators of metabolism, we sought to determine in biopsies from lean and obese aging rhesus monkeys the nature of defects in insulin ...

Endothelial insulin resistance is tightly associated with diabetic cardiovascular complication, and it is well known that inflammation plays an important role in the development of insulin resistance. Luteolin, a flavonoid abundant in some medical and eatable plants, is a potent inhibitor of inflammation. It is also reported that luteolin exhibited ...

Insulin signaling has been suggested, at least in part, to be affected by an insulin-mimetic species of low molecular weight. These inositol phosphoglycans (IPGs) are generated upon growth hormone/cytokine stimulation and control the activity of a multitude of insulin effector enzymes. The minimal structural requirements of IPGs for insulin-mimetic action ...

To explore the effect of LYRM1 over-expression on basal and insulin-stimulated glucose uptake in rat skeletal muscle cells, and to understand the underlying mechanisms, Rat myoblasts (L6) transfected with either an empty expression vector (pcDNA3.1Myc/His B) or a LYRM1 expression vector were differentiated into myotubes. Glucose uptake was determined by ...

Glutamate dehydrogenase (GDH) has been extensively studied for more than 50 years. Of particular interest is the fact that, while considered by most to be a 'housekeeping' enzyme, the animal form of GDH is heavily regulated by a wide array of allosteric effectors and exhibits extensive inter-subunit communication. While the ...

Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites produced by cytochrome P450 epoxygenases which are highly expressed in hepatocytes. The functions of EETs in hepatocytes are not well understood. In this study, we investigated the effects of 14,15-EETs treatment on the insulin signal transduction pathway in hepatocytes. We report that chronic ...

In an attempt to discover novel adipokines, we performed proteomics analyses using culture medium from differentiated 3T3-L1 adipocytes, and first identified GM2AP. The levels of GM2AP mRNA and protein were augmented by adipogenesis in cultured adipocytes and expression in adipose tissue and serum of obese mice or human subjects was ...

Substantial evidence suggests a link between elevated inflammation and development of insulin resistance. Toll-like receptor 2 (TLR2) recognises a large number of lipid-containing molecules and transduces inflammatory signalling in a variety of cell types, including insulin-responsive cells. Considering the contribution of the fatty acid composition in TLR2-depedent signalling, we hypothesised ...

Plasma C-reactive protein (CRP) concentration is increased in the metabolic syndrome, which consists of a cluster of cardiovascular disease risk factors, including insulin resistance. It is not known, however, whether CRP is merely a marker of accompanying inflammation or whether it contributes causally to insulin resistance. The objective of this ...

Cancer can be cured by platinum-based chemotherapy, but resistance is a major cause of treatment failure. Here we present the nematode Caenorhabditis elegans as a model to study interactions between the platinum drug cisplatin and signaling pathways in vivo. Null mutation in a single gene, asna-1, makes worms hypersensitive to ...

activity of the large conductance Ca(2+)-activated K(+) (BK) channels is profoundly modulated by its β(1) subunit (BK-β(1)). However, BK-β(1) expression is downregulated in diabetic vessels. The ubiquitin-proteasome system (UPS) is a major mechanism of intracellular protein degradation. Whether UPS participates in BK-β(1) downregulation in diabetic vessels is unknown. we hypothesize ...

A hyperglycemic environment in utero reduces kidney size and nephron number due to nascent nephron apoptosis. However, the underlying mechanisms are incompletely understood. The present study investigated whether the nascent nephron apoptosis promoted by high glucose is mediated via the transcription factor NF-κB and p53 signaling pathways. Neonatal mouse kidneys ...

The Akt signalling pathway plays vital roles in controlling cellular responses to insulin as well as in proliferation and survival. Inhibition of Akt signalling leads to insulin resistance and type 2 diabetes, whereas hyperactivation of Akt promotes tumorigenesis. In this study, we investigate how modest changes in the activity of ...

Ataxia telangiectasia (A-T) patients can develop multiple clinical pathologies, including neuronal degeneration, an elevated risk of cancer, telangiectasias, and growth retardation. Patients with A-T can also exhibit an increased risk of insulin resistance and type 2 diabetes. The ATM protein kinase, the product of the gene mutated in A-T patients ...

Background: Diabetic patients are at high risk to develop atherosclerotic cardiovascular disease and have a higher restenotic rate after percutaneous coronary intervention (PCI). Statins improve cardiovascular outcome and reduce restenosis after PCI by inhibiting proliferation and migration of vascular smooth muscle cells (VSMCs). But the effect of statins on diabetes ...

Identified as a major pathway controlling entry in the facultative dauer diapause stage, the DAF-2/Insulin receptor (InsR) signaling acts in multiple developmental and physiological regulation events in Caenorhabditis elegans. Here we identified a role of the insulin-like pathway in controlling developmental speed during the C. elegans second larval stage. This ...

Objective:Pigment epithelium-derived factor (PEDF) is a multifunctional protein with neurotrophic and anti-angiogenic properties. More recently it became evident that PEDF is upregulated in patients with type 2 diabetes and also contributes to insulin resistance in mice. During characterization of the secretome of in vitro differentiated human adipocytes by two-dimensional polyacrylamide ...

Adenosine triphosphate (ATP), an important signaling molecule, participates in various pathophysiological processes via the activation of purinergic-receptors. Recent studies have shown that the expression and function of purinergic-receptors (P2-receptors) could be altered in diabetic or hyperinsulinemia conditions. To characterize the effect of ATP on insulin signaling, we treated primary rat ...

Andrographolide (AG), the primary bioactive component of Andrographils paniculate Nees, has showed an anti-diabetic effect. However, the molecular mechanism has not been clarified. In this study, we demonstrated that AG increased glucose uptake in 3T3-L1 cells in a time- and dosedependent manner. The activation of insulin signaling by AG was ...

We compared mitogenicity and intracellular signalling by human insulin and the AspB10 (X-10) human insulin analogue in MCF-7 human mammary adenocarcinoma cells. By flow analysis of phosphorylated histone H3 or cell cycle distributions, insulin and X-10 were mitogenic at physiologically relevant concentrations (2 nm to 74 pm range), with X-10 being approximately ...

Insulin resistance is associated with chronic low-grade inflammation in vivo, largely mediated by activated innate immune cells. Cytokines and pathogen-derived ligands of surface toll-like receptors can directly cause insulin resistance in muscle cells. However, it is not known if intracellular pathogen sensors can, on their own, provoke insulin resistance. Here, ...

Diabetic nephropathy (DN) is the leading cause of renal failure in the world. It is characterized by albuminuria and abnormal glomerular function and is considered a hyperglycemic "microvascular" complication of diabetes, implying a primary defect in the endothelium. However, we have previously shown that human podocytes have robust responses to ...

A dynamic cycle of O-linked GlcNAc (O-GlcNAc) addition and removal is catalyzed by O-GlcNAc transferase and O-GlcNAcase, respectively, in a process that serves as the final step in a nutrient-driven "hexosamine-signaling pathway." Evidence points to a role for O-GlcNAc cycling in diabetes and insulin resistance. We have used Drosophila melanogaster ...

1. It is known that high glucose can induce cardiomyocyte apoptosis and that macrophage migration inhibitory factor (MIF) may be involved in the development of diabetes. However, the relationship between high glucose and MIF in diabetic cardiomyopathy remains unclear. 2. In the present study, AC16 human cardiomyocytes were cultured in ...

OBJECTIVES: 17β-oestradiol interacts with growth factors to modulate lactotroph cell population. However, contribution of isoforms of the oestrogen receptor in these activities is not fully understood. In the present study, we have established participation of α and β oestrogen receptors in effects of 17β-oestradiol on lactotroph proliferation induced by insulin ...

Obesity has been characterized as a state of chronic inflammation. Inflammatory signaling not only causes peripheral insulin resistance, but also promotes neuronal insulin and leptin resistance, which further propagates a positive energy balance. Upon development of obesity, numerous conditions, including increased circulating cytokine concentrations and cell autonomous dysregulation of homeostatic ...

Intimal hyperplasia (IH) exerts a critical role in vein graft failure after arterial bypassing. Insulin has been demonstrated to remarkably decrease IH in the rat carotid injury model. We hypothesized that postoperative insulin medication prevents the autologous vein graft from IH. Dogs were subjected to jugular-carotid interposition bypass grafting and ...

O-linked-β-N-acetylglucosamine (O-GlcNAc) modification is a regulatory, nuclear and cytoplasmic post-translational glycosylation of proteins associated with age-related diseases such as Alzheimer's, Parkinson's, and type II diabetes. Global elevation of O-GlcNAc levels on intracellular proteins can induce insulin resistance, the hallmark of type II diabetes, in mammalian systems. InC. elegans, attenuation of ...

Insulin-induced Na(+) retention in the distal nephron may contribute to the development of oedema/hypertension in patients with type 2 diabetes. This response to insulin is usually attributed to phosphatidylinositol-3-kinase (PI3K)/serum and glucocorticoid-inducible kinase 1 (SGK1) but a role for protein kinase B (PKB) has been proposed. The present study therefore ...

Excessive proliferation of vascular smooth muscle cells (VSMCs), which migrate from the tunica media to the subendothelial region, is one of the primary lesions involved in atherogenesis in diabetes. Here, we investigated whether high glucose potentiated the proliferation and chemotaxis of VSMCs by activating SDF-1α/CXCR4/PI-3K/Akt signalling. The expression of SDF-1α, ...

Mammalian DOR was discovered as a gene whose expression is misregulated in muscle of Zucker diabetic rats. Because no DOR loss-of-function mammalian models are available, we analyze here the in vivo function of DOR by studying flies mutant for Drosophila DOR (dDOR). We show that dDOR is a novel coactivator of ...

Insulin resistance plays an important role in the development of type 2 diabetes mellitus. Scopoletin, a phenolic coumarin, is reported to regulate hyperglycemia and diabetes. To examine its effect on insulin resistance, we treated high-glucose-induced, insulin-resistant HepG2 cells with scopoletin and measured phosphatidylinositol 3-kinase (PI3 K)-linked protein kinase B (Akt/PKB) phosphorylation. ...

The inhibition of protein tyrosine phosphatase 1B (PTP1B) is of substantial interest for the treatment of type-2 diabetes mellitus. Using an in vitro enzyme assay with human recombinant PTP1B 1,2,3,4,6-penta-O-galloyl-D-glucopyranose was isolated from the roots of Paeonia lactiflora as an inhibitor of PTP1B, with an IC(50) value of 4.8 μM. ...

We investigated the function of the Prep1 gene in insulin-dependent glucose homeostasis in liver. Prep1 action on insulin glucoregulatory function has been analyzed in liver of Prep1-hypomorphic mice (Prep1(i/i)), which express 2-3% of Prep1 mRNA. Based on euglycemic hyperinsulinemic clamp studies and measurement of glycogen content, livers from Prep1(i/i) mice ...

We infused the 48h intralipid plus heparin (IH) to normal rats to elevate plasma free fatty acids (FFAs). Co-infusion of taurine was designed for the purpose of studying the effects of taurine on insulin sensitivity, oxidative stress, c-Jun NH-terminal kinase (JNK)1 activity and insulin signaling in livers of prolonged IH-infused ...

Components of the insulin receptor signaling pathway are probably some of the best studied ones. Even though methods for studying these components are well established, the in vivo effects of different fasting regimens, and the time course of insulin receptor phosphorylation and that of its downstream components in insulin-sensitive peripheral ...

Insulin receptor substrate-1 (IRS-1) plays a pivotal role in insulin signaling, therefore its degradation is exquisitely regulated. Here, we show that insulin-stimulated degradation of IRS-1 requires the presence of a highly conserved Ser/Thr-rich domain that we named domain involved in degradation of IRS-1 (DIDI). DIDI (amino acids 386-430 of IRS-1) ...

Cells can not only sense the type of extracellular matrix (ECM) protein that is present in the microenvironment, but they can also sense its density. Here, we investigated the effects of ECM protein density on adipokine secretion and insulin signaling in adipocytes. To this end, 3T3-L1 adipocytes were cultured on ...

The Src homology 2 domain-containing protein-tyrosine phosphatase Shp2 has been implicated in a variety of growth factor signaling pathways, but its role in insulin signaling has remained unresolved. In vitro studies suggest that Shp2 is both a negative and positive regulator of insulin signaling, although its physiological function in a ...

Diabetes mellitus is a systemic disease responsible for morbidity in the western world and is gradually becoming prevalent in developing countries too. The prevalence of diabetes is rapidly increasing in industrialized countries and type 2 diabetes accounts for 90% of the disease. Insulin resistance is a major pathophysiological factor in ...

Organismal lifespan can be extended by genetic manipulation of cellular processes such as histone acetylation, the insulin/IGF-1 (insulin-like growth factor 1) pathway or the p53 system. Longevity-promoting regimens, including caloric restriction and inhibition of TOR with rapamycin, resveratrol or the natural polyamine spermidine, have been associated with autophagy (a cytoprotective ...

Activation of stress-kinase signaling has recently been recognized as an important pathophysiological mechanism in the development of diet-induced obesity, type 2 diabetes mellitus and other aging-related pathologies. Here, c-Jun N-terminal Kinase (JNK) 1 knockout mice have been shown to exhibit protection from diet-induced obesity, glucose intolerance, and insulin resistance. Nonetheless, ...

Serum starvation is a common cell culture procedure for increasing cellular response to insulin, though the mechanism for the serum starvation effect is not understood. We hypothesized that factors known to potentiate insulin action [e.g., AMP-activated protein kinase (AMPK) and p38] or to be involved in insulin signaling leading to ...

Insulin inhibits ischemia/reperfusion-induced myocardial apoptosis through the activation of a survival signaling cascade including the phosphatidylinositol 3-kinase (PI3K)-Akt pathway. However, the down-stream mechanism of PI3K remains elusive. This study is aimed at investigating whether survivin (SVV) plays a role in the insulin-induced anti-apoptotic effect in the ischemic/reperfused (I/R) hearts, and ...

Classical actions of insulin involve increased glucose uptake from the bloodstream and its metabolism in peripheral tissues, the most important and relevant effects for human health. However, nonoxidative and oxidative glucose disposal by activation of glycogen synthase (GS) and mitochondrial pyruvate dehydrogenase (PDH) remain incompletely explained by current models for ...