Cocaine- and amphetamine-regulated transcript is expressed in adipocytes and regulate lipid- and glucose homeostasis.

Cocaine- and amphetamine-regulated transcript (CART) is a regulatory peptide expressed in the nervous system and in endocrine cells, e.g. in pancreatic islets. CART deficient mice exhibit islet dysfunction, impaired insulin secretion and increased body weight. A mutation in the CART gene in humans is associated with reduced metabolic rate, obesity and diabetes. Furthermore, CART is upregulated in islets of type-2 diabetic rats and regulates islet hormone secretion in vitro. While the function of CART in the nervous system has been extensively studied, there is no information on its expression or function in white adipose tissue. CART mRNA and protein were found to be expressed in both subcutaneous and visceral white adipose tissues from rat and man. Stimulating rat primary adipocytes with CART significantly potentiated isoprenaline-induced lipolysis, and hormone sensitive lipase activation (phosphorylation of Ser 563). On the other hand, CART significantly potentiated the inhibitory effect of insulin on isoprenaline-induced lipolysis. CART inhibited insulin-induced glucose uptake, which was associated with inhibition of PKB phosphorylation. In conclusion, CART is a novel constituent of human and rat adipocytes and affects several biological processes central in both lipid- and glucose homeostasis. Depending on the surrounding conditions, the effects of CART are insulin-like or insulin-antagonistic

A Role for Phosphodiesterase 3B in Acquisition of Brown Fat Characteristics by White Adipose Tissue in Male Mice.

Obesity is linked to various diseases, including insulin resistance, diabetes, and cardiovascular disorders. The idea of inducing white adipose tissue (WAT) to assume characteristics of brown adipose tissue (BAT), and thus gearing it to fat-burning instead of storage, is receiving serious consideration as potential treatment for obesity and related disorders. Phosphodiesterase 3B (PDE3B) links insulin- and cAMP-signaling networks in tissues associated with energy metabolism, including WAT. We utilized C57BL/6 PDE3B knockout (KO) mice to elucidate mechanisms involved in the formation of BAT in epididymal WAT (EWAT) depots. Examination of gene expression profiles in PDE3B KO EWAT revealed increased expression of several genes that block white and promote brown adipogenesis, such as C-terminal binding protein (Ctbp), bone morphogenetic protein 7 (Bmp7) and PR domain containing 16 (Prdm16), but a clear BAT-like phenotype was not completely induced. However, acute treatment of PDE3B KO mice with the β3-adrenergic agonist, CL316243, markedly increased expression of cyclooxygenase-2 (COX-2), which catalyzes prostaglandin synthesis and is thought to be important in formation of BAT in WAT, and of elongation of very long chain fatty acids 3 (Elovl3), which is linked to BAT recruitment upon cold exposure, causing a clear shift toward fat-burning and induction of BAT in KO EWAT. These data provide insight into mechanisms of BAT formation in mouse EWAT, suggesting that, in C57BL/6 background, an increase in cAMP, caused by ablation of PDE3B and administration of CL316243, may promote differentiation of prostaglandin-responsive progenitor cells in the EWAT stromal vascular fraction into functional brown adipocytes

Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes.

Reduced insulin release has been linked to defect exocytosis in β-cells. However, whether expression of genes suggested to be involved in the exocytotic process (exocytotic genes) is altered in pancreatic islets from patients with type 2 diabetes (T2D), and correlate to insulin secretion, needs to be further investigated. Analysing expression levels of 23 exocytotic genes using microarray revealed reduced expression of five genes in human T2D islets (χ(2)=13.25; p<0.001). Gene expression of STX1A, SYT4, SYT7, SYT11, SYT13, SNAP25 and STXBP1 correlated negatively to in vivo measurements of HbA1c levels and positively to glucose stimulated insulin secretion (GSIS) in vitro in human islets. STX1A, SYT4 and SYT11 protein levels correspondingly decreased in human T2D islets. Moreover, silencing of SYT4 and SYT13 reduced GSIS in INS1-832/13 cells. Our data support that reduced expression of exocytotic genes contributes to impaired insulin secretion, and suggest decreased expression of these genes as part of T2D pathogenesis

Разработка инвестиционного проекта «Пасека» в развитии агротуризма

Материалы V Междунар. науч. конф. студентов, аспирантов и молодых ученых, Гомель, 24 мая 2012

Expression and Regulation of Cyclic Nucleotide Phosphodiesterases in Human and Rat Pancreatic Islets

As shown by transgenic mouse models and by using phosphodiesterase 3 (PDE3) inhibitors, PDE3B has an important role in the regulation of insulin secretion in pancreatic β-cells. However, very little is known about the regulation of the enzyme. Here, we show that PDE3B is activated in response to high glucose, insulin and cAMP elevation in rat pancreatic islets and INS-1 (832/13) cells. Activation by glucose was not affected by the presence of diazoxide. PDE3B activation was coupled to an increase as well as a decrease in total phosphorylation of the enzyme. In addition to PDE3B, several other PDEs were detected in human pancreatic islets: PDE1, PDE3, PDE4C, PDE7A, PDE8A and PDE10A. We conclude that PDE3B is activated in response to agents relevant for β-cell function and that activation is linked to increased as well as decreased phosphorylation of the enzyme. Moreover, we conclude that several PDEs are present in human pancreatic islets

Phosphodiesterase 3B Is Localized in Caveolae and Smooth ER in Mouse Hepatocytes and Is Important in the Regulation of Glucose and Lipid Metabolism

Cyclic nucleotide phosphodiesterases (PDEs) are important regulators of signal transduction processes mediated by cAMP and cGMP. One PDE family member, PDE3B, plays an important role in the regulation of a variety of metabolic processes such as lipolysis and insulin secretion. In this study, the cellular localization and the role of PDE3B in the regulation of triglyceride, cholesterol and glucose metabolism in hepatocytes were investigated. PDE3B was identified in caveolae, specific regions in the plasma membrane, and smooth endoplasmic reticulum. In caveolin-1 knock out mice, which lack caveolae, the amount of PDE3B protein and activity were reduced indicating a role of caveolin-1/caveolae in the stabilization of enzyme protein. Hepatocytes from PDE3B knock out mice displayed increased glucose, triglyceride and cholesterol levels, which was associated with increased expression of gluconeogenic and lipogenic genes/enzymes including, phosphoenolpyruvate carboxykinase, peroxisome proliferator-activated receptor γ, sterol regulatory element-binding protein 1c and hydroxyl-3-methylglutaryl coenzyme A reductase. In conclusion, hepatocyte PDE3B is localized in caveolae and smooth endoplasmic reticulum and plays important roles in the regulation of glucose, triglyceride and cholesterol metabolism. Dysregulation of PDE3B could have a role in the development of fatty liver, a condition highly relevant in the context of type 2 diabetes

Tablet's role in communication and participation : The staff's experience of the tablet in the special school orientation training school with a focus on communication and participation

Denna studie är en enkätstudie med syfte att undersöka hur personal i grundsärskolor med inriktning träningsskola runt om i landet använder surfplattan i verksamheten. Om surfplattan kan vara ett stöd för kommunikation och om detta kan leda till delaktighet. Vi utgår från följande frågeställningar.   -          Vilken erfarenhet har personal  av surfplattan som kommunikationsverktyg i grundsärskolans inriktning träningsskola? -          Hur används surfplattan för att skapa delaktighet för eleverna i grundsärskolans inriktning träningsskola? Vid analysen har vi tittat på resultaten kring kommunikation ur ett sociokulturellt perspektiv samt utifrån Claude Shannon och Warren Weavers teori inom kommunikation. Vi har även analyserat utifrån Kristina Szönyi och Tove Söderqvist Dunkers modell kring delaktighet.   Studien visar på att surfplattan anses som ett bra verktyg för kommunikation främst inom ämnesområdet kommunikation. Den används till stor del som stöd i undervisningen men även som ett dokumentationsverktyg som främjar kommunikationen mellan skolan och hemmet. Studien visar även på att det finns flera fördelar med att använda surfplattan för att skapa möjlighet till delaktighet hos eleven och då främst genom kommunikation.

Cyclic nucleotide phosphodiesterases (PDEs): diverse regulators of cyclic nucleotide signals and inviting molecular targets for novel therapeutic agents

Introduction: Cyclic adenosine 3’5’-monophosphate (cAMP) and cyclic guanosine 3’5’-monophoshpate (cGMP) are critical intracellular second-messengers involved in the transduction of a wide variety of extracellular stimuli, including peptide hormones, growth factors, cytokines, neurotransmitters and light. These messengers modulate many fundamental biological processes, including growth, differentiation, apoptosis, glycogenolysis, lipolysis, immune/inflammatory responses, etc. By catalyzing hydrolysis of cAMP and cGMP, cyclic nucleotide phosphodiesterases (PDEs) are important determinants in regulating the intracellular concentrations and, consequently, the biological actions of these second-messengers (Fig. 1). The advent of molecular genetics has revealed the extraordinary complexity and diversity of the mammalian PDE superfamily, which contains at least 10 highly regulated and structurally-related gene families (PDEs 1-10).1-8 As depicted in Figure 1, some PDEs are highly specific for hydrolysis of cAMP (PDEs 4,7,8), some are cGMP-specific (PDEs 5,6,9), and some exhibit mixed specificity (PDEs 1,2,3,10). Most gene families are comprised of more than one isogene (indicated by A-D in Table 1). At least 19 genes encoding more than 30 isoforms have been identified. PDE families differ with respect to their primary structures, sensitivity to specific inhibitors, tissue distribution, subcellular localization, and mechanisms of regulation (Table 1).2-6 Within individual families, different mRNAs are generated from the same gene by use of different transcription initiation sites or by alternative mRNA splicing. These variant PDE isoforms are often tissue-specific and selectively expressed in various tissues and cell types.2-6 The importance of cyclic nucleotide signaling in cell regulation and the molecular diversity of PDEs has presented targets for selective interventions and development of family-specific PDE inhibitors as therapeutic agents. This brief review will discuss some general characteristics of PDEs and then focus on the cellular biology and diverse functions of different PDE isoforms and their potential as therapeutic targets

AMPKβ isoform expression patterns in various adipocyte models and in relation to body mass index

AMP-activated protein kinase (AMPK) activation is considered a useful strategy for the treatment of type 2 diabetes (T2D). It is unclear whether the expression and/or activity of AMPK in adipocytes is dysregulated in obesity. Also, the expression/activity pattern of AMPKβ isoforms, which are targets for AMPK activators, in adipocytes remains elusive. In this study we show that the two AMPKβ isoforms make roughly equal contributions to AMPK activity in primary human and mouse adipocytes, whereas in cultured 3T3-L1 adipocytes of mouse origin and in primary rat adipocytes, β1-associated activity clearly dominates. Additionally, we found that obesity is not associated with changes in AMPK subunit expression or kinase activity in adipocytes isolated from subcutaneous adipose tissue from individuals with various BMI