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https://www.readbyqxmd.com/read/27896318/insulin-elevates-leptin-secretion-and-mrna-levels-via-cyclic-amp-in-3t3-l1-adipocytes-deprived-of-glucose
#1
Tomomi Tsubai, Yukihiro Noda, Kazuma Ito, Makoto Nakao, Yusuke Seino, Yutaka Oiso, Yoji Hamada
AIMS: Leptin plays an important role in the pathogenesis of obesity and diabetes, yet the regulatory mechanisms of this hormone have not been fully elucidated. In this study, we aimed to clarify the roles of insulin and glucose in leptin secretion and mRNA production using inhibitors of insulin signal transduction in adipocytes cultured under glucose-free or normal conditions. METHODS: Differentiated 3T3-L1 adipocytes were stimulated with insulin in combination with inhibitors for phosphoinositide 3-kinase (PI3K), Akt, and phosphodiesterase 3B (PDE3B), as well as epinephrine and a cyclic AMP (cAMP) analog under glucose-free or normal conditions...
November 2016: Heliyon
https://www.readbyqxmd.com/read/27867269/platyphylloside-isolated-from-betula-platyphylla-inhibit-adipocyte-differentiation-and-induce-lipolysis-via-regulating-adipokines-including-ppar%C3%AE-in-3t3-l1-cells
#2
Mina Lee, Sang Hyun Sung
BACKGROUND: Obesity causes or aggravates many health problems, both independently and in association with several pathological disorders, including Type II diabetes, hypertension, atherosclerosis, and cancer. Therefore, we screened small compounds isolated from natural products for the development of anti-obesity drugs. OBJECTIVE: The purpose of this study was to investigate the anti-adipogenic activities of platyphylloside, diarylheptanoid isolated from Betula platyphylla, which was selected based on the screening using 3T3-L1 cells...
October 2016: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/27865066/newly-synthesized-camp-is-integrated-at-a-membrane-protein-complex-signalosome-to-ensure-receptor-response-specificity
#3
Raquel Guinzberg, Antonio Díaz-Cruz, Carlos Acosta-Trujillo, María Magdalena Vilchis-Landeros, Héctor Vázquez-Meza, Carlos Lozano-Flores, Natalia Chiquete-Felix, Alfredo Varela-Echavarría, Salvador Uribe-Carvajal, Héctor Riveros-Rosas, Enrique Piña
Spatiotemporal regulation of cAMP within the cell is required to achieve receptor-specific responses. The mechanism through which the cell selects a specific response to new synthesized cAMP is not fully understood. In hepatocyte plasma membranes, we identified two functional and independent cAMP-responsive signaling protein macrocomplexes that produce, use, degrade, and regulate their own non-diffusible (sequestered) cAMP pool to achieve their specific responses. Each complex responds to the stimulation of an adenosine G-protein coupled receptor (Ado-GPCR), bound to either A2A or A2B , but not simultaneously to both...
November 19, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27720677/phagocytosis-of-bone-marrow-derived-macrophages-is-controlled-by-phosphoinositide-3-kinase-%C3%AE
#4
Anne Kresinsky, Nadine Schneble, Caroline Schmidt, Adrian Frister, Reinhard Bauer, Reinhard Wetzker, Jörg P Müller
Due to their ability to phagocytise invading microbes macrophages play a key role in the innate and acquired immune system. In this article the role of phosphoinositide 3-kinase gamma (PI3Kγ) for phagocytosis was studied in bone marrow derived macrophages (BMDM). By using genetic and pharmacological approaches our data clearly demonstrate PI3Kγ is acting as a mediator of macrophage phagocytosis. Phagocytosis of LPS activated BMDM was reduced in PI3Kγ depleted primary BMDM or macrophage cell line J774. Depletion of other class I phosphoinositide 3-kinases did not alter phagocytic activity...
October 5, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27696085/transcriptomic-effects-of-adenosine-2a-receptor-deletion-in-healthy-and-endotoxemic-murine-myocardium
#5
Kevin J Ashton, Melissa E Reichelt, S Jamal Mustafa, Bunyen Teng, Catherine Ledent, Lea M D Delbridge, Polly A Hofmann, R Ray Morrison, John P Headrick
Influences of adenosine 2A receptor (A2AR) activity on the cardiac transcriptome and genesis of endotoxemic myocarditis are unclear. We applied transcriptomic profiling (39 K Affymetrix arrays) to identify A2AR-sensitive molecules, revealed by receptor knockout (KO), in healthy and endotoxemic hearts. Baseline cardiac function was unaltered and only 37 A2AR-sensitive genes modified by A2AR KO (≥1.2-fold change, <5 % FDR); the five most induced are Mtr, Ppbp, Chac1, Ctsk and Cnpy2 and the five most repressed are Hp, Yipf4, Acta1, Cidec and Map3k2...
September 30, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27685753/inhibition-of-phosphodiesterase-3-4-and-5-induces-endolymphatic-hydrops-in-mouse-inner-ear-as-evaluated-with-repeated-9-4t-mri
#6
Eva Degerman, Rene In 't Zandt, Annki Pålbrink, Lena Eliasson, Per Cayé-Thomasen, Måns Magnusson
CONCLUSION: The data indicate important roles for phosphodiesterase (PDE) 3, 4, 5, and related cAMP and cGMP pools in the regulation of inner ear fluid homeostasis. Thus, dysfunction of these enzymes might contribute to pathologies of the inner ear. OBJECTIVE: The mechanisms underlying endolymphatic hydrops, a hallmark of inner ear dysfunction, are not known in detail; however, altered balance in cAMP and cGMP signaling systems appears to be involved. Key components of these systems are PDEs, enzymes that modulate the amplitude, duration, termination, and specificity of cAMP and cGMP signaling...
August 15, 2016: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/27544668/filarial-infection-or-antigen-administration-improves-glucose-tolerance-in-diet-induced-obese-mice
#7
Afiat Berbudi, Jayagopi Surendar, Jesuthas Ajendra, Fabian Gondorf, David Schmidt, Anna-Lena Neumann, Ajeng P F Wardani, Laura E Layland, Linda S Hoffmann, Alexander Pfeifer, Achim Hoerauf, Marc P Hübner
Helminths induce type 2 immune responses and establish an anti-inflammatory milieu in their hosts. This immunomodulation was previously shown to improve diet-induced insulin resistance which is linked to chronic inflammation. In the current study, we demonstrate that infection with the filarial nematode Litomosoides sigmodontis increased the eosinophil number and alternatively activated macrophage abundance within epididymal adipose tissue (EAT) and improved glucose tolerance in diet-induced obese mice in an eosinophil-dependent manner...
August 20, 2016: Journal of Innate Immunity
https://www.readbyqxmd.com/read/27343375/metformin-and-resveratrol-ameliorate-muscle-insulin-resistance-through-preventing-lipolysis-and-inflammation-in-hypoxic-adipose-tissue
#8
Wenjun Zhao, Aiyun Li, Xin Feng, Ting Hou, Kang Liu, Baolin Liu, Ning Zhang
This study aims to investigate the effects of metformin and resveratrol on muscle insulin resistance with emphasis on the regulation of lipolysis in hypoxic adipose tissue. ICR mice were fed with high fat diet (HFD) for 10days with administration of metformin, resveratrol, or intraperitoneal injection of digoxin. Adipose hypoxia, inflammation and cAMP/PKA-dependent lipolysis were investigated. Moreover, lipid deposition and insulin resistance were examined in the muscle. Metformin and resveratrol attenuated adipose hypoxia, inhibited HIF-1α expression and inflammation in the adipose tissue of HFD-fed mice...
September 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27321128/phosphodiesterase-3b-pde3b-regulates-nlrp3-inflammasome-in-adipose-tissue
#9
Faiyaz Ahmad, Youn Wook Chung, Yan Tang, Steven C Hockman, Shiwei Liu, Yusuf Khan, Kevin Huo, Eric Billings, Marcelo J Amar, Alan T Remaley, Vincent C Manganiello
Activation of inflammation in white adipose tissue (WAT), includes infiltration/expansion of WAT macrophages, contributes pathogenesis of obesity, insulin resistance, and metabolic syndrome. The inflammasome comprises an intracellular sensor (NLR), caspase-1 and the adaptor ASC. Inflammasome activation leads to maturation of caspase-1 and processing of IL1β, contributing to many metabolic disorders and directing adipocytes to a more insulin-resistant phenotype. Ablation of PDE3B in WAT prevents inflammasome activation by reducing expression of NLRP3, caspase-1, ASC, AIM2, TNFα, IL1β and proinflammatory genes...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27272565/copper-regulates-cyclic-amp-dependent-lipolysis
#10
Lakshmi Krishnamoorthy, Joseph A Cotruvo, Jefferson Chan, Harini Kaluarachchi, Abigael Muchenditsi, Venkata S Pendyala, Shang Jia, Allegra T Aron, Cheri M Ackerman, Mark N Vander Wal, Timothy Guan, Lukas P Smaga, Samouil L Farhi, Elizabeth J New, Svetlana Lutsenko, Christopher J Chang
Cell signaling relies extensively on dynamic pools of redox-inactive metal ions such as sodium, potassium, calcium and zinc, but their redox-active transition metal counterparts such as copper and iron have been studied primarily as static enzyme cofactors. Here we report that copper is an endogenous regulator of lipolysis, the breakdown of fat, which is an essential process in maintaining body weight and energy stores. Using a mouse model of genetic copper misregulation, in combination with pharmacological alterations in copper status and imaging studies in a 3T3-L1 white adipocyte model, we found that copper regulates lipolysis at the level of the second messenger, cyclic AMP (cAMP), by altering the activity of the cAMP-degrading phosphodiesterase PDE3B...
August 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27255754/rna-binding-protein-cugbp1-regulates-insulin-secretion-via-activation-of-phosphodiesterase-3b-in-mice
#11
Kui Zhai, Lei Gu, Zhiguang Yang, Yang Mao, Meng Jin, Yan Chang, Qi Yuan, Veronique Leblais, Huiwen Wang, Rodolphe Fischmeister, Guangju Ji
AIMS/HYPOTHESIS: CUG-binding protein 1 (CUGBP1) is a multifunctional RNA-binding protein that regulates RNA processing at several stages including translation, deadenylation and alternative splicing, as well as RNA stability. Recent studies indicate that CUGBP1 may play a role in metabolic disorders. Our objective was to examine its role in endocrine pancreas function through gain- and loss-of-function experiments and to further decipher the underlying molecular mechanisms. METHODS: A mouse model in which type 2 diabetes was induced by a high-fat diet (HFD; 60% energy from fat) and mice on a standard chow diet (10% energy from fat) were compared...
September 2016: Diabetologia
https://www.readbyqxmd.com/read/27220352/curcumin-inhibits-lipolysis-via-suppression-of-er-stress-in-adipose-tissue-and-prevents-hepatic-insulin-resistance
#12
Lulu Wang, Bangling Zhang, Fang Huang, Baolin Liu, Yuan Xie
Curcumin is natural polyphenol with beneficial effects on lipid and glucose metabolism and this study aimed to investigate the effects of curcumin on lipolysis and hepatic insulin resistance. Endoplasmic reticulum (ER) stress and lipolysis signaling in adipose and FFA influx, lipid deposits, and glucose production in liver were examined. Palmitate challenge and high-fat diet feeding evoked ER stress-associated lipolysis with cAMP accumulation in adipose tissue. Curcumin treatment inhibited adipose tissue ER stress by dephosphorylation of inositol-requiring enzyme 1α and eukaryotic initiation factor 2α and reduced cAMP accumulation by preserving phosphodiesterase 3B induction...
July 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27108947/novel-approaches-to-targeting-pde3-in-cardiovascular-disease
#13
REVIEW
Matthew Movsesian
Inhibitors of PDE3, a family of dual-specificity cyclic nucleotide phosphodiesterases, are used clinically to increase cardiac contractility by raising intracellular cAMP content in cardiac myocytes and to reduce vascular resistance by increasing intracellular cGMP content in vascular smooth muscle myocytes. When used in the treatment of patients with heart failure, PDE3 inhibitors are effective in the acute setting but increase sudden cardiac death with long-term administration, possibly reflecting pro-apoptotic and pro-hypertrophic consequences of increased cAMP-mediated signaling in cardiac myocytes...
July 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27002827/hypothalamic-phosphodiesterase-3b-pathway-mediates-anorectic-and-body-weight-reducing-effects-of-insulin-in-male-mice
#14
Maitrayee Sahu, Prashanth Anamthathmakula, Abhiram Sahu
BACKGROUND: Insulin action in the hypothalamus plays a critical role in the regulation of energy homeostasis, yet the intracellular signaling mechanisms mediating insulin action are incompletely understood. Although phosphodiesterase-3B (PDE3B) mediates insulin action in the adipose tissue and it is highly expressed in the hypothalamic areas implicated in energy homeostasis, its role, if any, in mediating insulin action in the hypothalamus is unknown. We tested the hypothesis that insulin action in the hypothalamus is mediated by PDE3B...
March 23, 2016: Neuroendocrinology
https://www.readbyqxmd.com/read/26938239/oxamate-improves-glycemic-control-and-insulin-sensitivity-via-inhibition-of-tissue-lactate-production-in-db-db-mice
#15
Weiran Ye, Yijia Zheng, Shanshan Zhang, Li Yan, Hua Cheng, Muchao Wu
Oxamate (OXA) is a pyruvate analogue that directly inhibits the lactate dehydrogenase (LDH)-catalyzed conversion process of pyruvate into lactate. Earlier and recent studies have shown elevated blood lactate levels among insulin-resistant and type 2 diabetes subjects and that blood lactate levels independently predicted the development of incident diabetes. To explore the potential of OXA in the treatment of diabetes, db/db mice were treated with OXA in vivo. Treatment of OXA (350-750 mg/kg of body weight) for 12 weeks was shown to decrease body weight gain and blood glucose and HbA1c levels and improve insulin secretion, the morphology of pancreatic islets, and insulin sensitivity in db/db mice...
2016: PloS One
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