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primary adipocyte diabetes

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https://www.readbyqxmd.com/read/29733303/an-in-ovo-model-for-testing-insulin-mimetic-compounds
#1
Renate Haselgrübler, Flora Stübl, Verena Stadlbauer, Peter Lanzerstorfer, Julian Weghuber
Elevated blood glucose levels in type 2 diabetes mellitus (T2DM), a complex and multifactorial metabolic disease, are caused by insulin resistance and β-cell failure. Various strategies, including the injection of insulin or the usage of insulin-sensitizing drugs, were pursued to treat T2DM or at least reduce the symptoms. In addition, the application of herbal compounds has attracted increasing attention. Thus, it is necessary to find efficient test systems to identify and characterize insulin-mimetic compounds...
April 23, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29724916/inhibition-of-foxo1-transcription-factor-in-primary-human-adipocytes-mimics-the-insulin-resistant-state-of-type-2-diabetes
#2
Meenu R Rajan, Elin Nyman, Cecilia Brännmark, Charlotta S Olofsson, Peter Strålfors
Type 2 diabetes is characterized by insulin resistance in the expanding adipose tissue of obesity. The insulin resistance manifests in human adipocytes as system-wide impairment of insulin signalling. An exception is regulation of transcription factor FOXO1, which is phosphorylated downstream of mTORC2 and is therefore not exhibiting impaired response to insulin. However, the abundance, and activity, of FOXO1 is reduced by half in adipocytes from patients with diabetes. To elucidate the effect of reduced FOXO1 activity, we herein transduced human adipocytes with a dominant-negative construct of FOXO1 (DN-FOXO1)...
May 3, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29705001/dendritic-peptide-bolaamphiphiles-for-sirna-delivery-to-primary-adipocytes
#3
Alexander C Eldredge, Mark E Johnson, Yang Cao, Lin Zhang, Can Zhao, Zhengxia Liu, Qin Yang, Zhibin Guan
Obesity is a major risk factor for diabetes, heart disease and other health problems. Adipose tissue plays a central role in the development of obesity and obesity-associated diseases. Gene therapy targeting adipose tissue may provide a promising strategy for obesity treatment. However, nucleic acid delivery to adipose tissue or even cultured adipocytes is challenging due to low delivery efficacy and high toxicity of the current cationic lipid based delivery systems, or monoamphiphiles. Herein, we report using dendritic peptide bolaamphiphiles (bolas) to deliver siRNA to primary adipocytes and hepatocytes...
April 16, 2018: Biomaterials
https://www.readbyqxmd.com/read/29689639/establishment-and-characterization-of-a-primary-murine-adipose-tissue-chip
#4
Nida Tanataweethum, Adelyn Zelaya, Feipeng Yang, Ronald N Cohen, Eric M Brey, Abhinav Bhushan
Better experimental models are needed to enhance our understanding of metabolic regulation which is seen in obesity and metabolic disorders, such as type 2 diabetes. In vitro models based on microfluidics enable physiological representations of tissues with several advantages over conventional culture systems, such as perfused flow to better mimic the physiological environment. Although cell lines such as 3T3-L1 have been incorporated in microfluidic devices, murine primary preadipocytes have not been differentiated and maintained for long-term monitoring in these culture systems...
April 24, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29589999/biguanides-metformin-and-phenformin-generate-therapeutic-effects-via-amp-activated-protein-kinase-extracellular-regulated-kinase-pathways-in-an-in-vitro-model-of-graves-orbitopathy
#5
Ye Eon Han, Sena Hwang, Jin Hee Kim, Jung Woo Byun, Jin Sook Yoon, Eun Jig Lee
BACKGROUND: It was hypothesized that the biguanides metformin and phenformin, which are anti-hyperglycemic drugs used for diabetes mellitus, would have therapeutic effects in an in vitro model of Graves' orbitopathy (GO). Because adipogenesis, hyaluronan production, and inflammation are considered important in the pathogenesis of GO, this study aimed to determine the therapeutic effects and underlying mechanisms of biguanides on these parameters. METHODS: In vitro experiments were performed using primary cultured orbital fibroblasts from patients with GO...
April 2018: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29522441/mir-146b-inhibits-glucose-consumption-by-targeting-irs1-gene-in-porcine-primary-adipocytes
#6
Yan-Ling Zhu, Ting Chen, Jia-Li Xiong, Di Wu, Qian-Yun Xi, Jun-Yi Luo, Jia-Jie Sun, Yong-Liang Zhang
Adipose tissue plays an important role in energy metabolism. Adipose dysfunction is closely related to obesity and type II diabetes. Glucose uptake is the key step for fat synthesis in adipocyte. miRNAs have been proven to play a crucial role in adipocyte differentiation, adipogenesis and glucose homeostasis. In this paper, we firstly reported that miR-146b decreased glucose consumption by up-regulating miR-146b in a porcine primary adipocyte model, while the inhibitor of endogenous miR-146b rescued the reduction...
March 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29514876/adipogenesis-in-fish
#7
REVIEW
Cristina Salmerón
White adipose tissue (AT) is the main lipid storage depot in vertebrates. Initially considered to be a simple lipid store, AT has recently been recognized as playing a role as an endocrine organ that is implicated in processes such as energy homeostasis and as a rich source of stem cells. Interest in adipogenesis has increased not only because of the prevalence of obesity, metabolic syndrome and type 2 diabetes in humans, but also in aquaculture because of the excessive fat deposition experienced in some cultured fish species, which may compromise both their welfare and their final product quality...
March 7, 2018: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29439250/hoxa5-promotes-adipose-differentiation-via-increasing-dna-methylation-level-and-inhibiting-pka-hsl-signal-pathway-in-mice
#8
Weina Cao, Yatao Xu, Dan Luo, Muhammad Saeed, Chao Sun
BACKGROUND/AIMS: Impaired adipogenesis may be the underlying cause in the development of obesity and type II diabetes. Mechanistically, the family of Homeobox transcription factors is implicated in the regulation of adipocyte fate. Hoxa5 is highly expressed in adipocytes, and its mRNA expression is decreased during differentiation. However, the function of Hoxa5 in adipose tissue has been poorly understood. The aim of this study is to unveil the role of Hoxa5 on adipocyte differentiation and its underlying mechanisms...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29379887/quercetin-inhibits-adipogenesis-of-muscle-progenitor-cells-in-vitro
#9
Tomoko Funakoshi, Noriyuki Kanzaki, Yuta Otsuka, Takayuki Izumo, Hiroshi Shibata, Shuichi Machida
Muscle satellite cells are committed myogenic progenitors capable of contributing to myogenesis to maintain adult muscle mass and function. Several experiments have demonstrated that muscle satellite cells can differentiate into adipocytes in vitro , supporting the mesenchymal differentiation potential of these cells. Moreover, muscle satellite cells may be a source of ectopic muscle adipocytes, explaining the lipid accumulation often observed in aged skeletal muscle (sarcopenia) and in muscles of patients` with diabetes...
March 2018: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29379070/the-transcriptional-response-to-oxidative-stress-is-part-of-but-not-sufficient-for-insulin-resistance-in-adipocytes
#10
Rima Chaudhuri, James R Krycer, Daniel J Fazakerley, Kelsey H Fisher-Wellman, Zhiduan Su, Kyle L Hoehn, Jean Yee Hwa Yang, Zdenka Kuncic, Fatemeh Vafaee, David E James
Insulin resistance is a major risk factor for metabolic diseases such as Type 2 diabetes. Although the underlying mechanisms of insulin resistance remain elusive, oxidative stress is a unifying driver by which numerous extrinsic signals and cellular stresses trigger insulin resistance. Consequently, we sought to understand the cellular response to oxidative stress and its role in insulin resistance. Using cultured 3T3-L1 adipocytes, we established a model of physiologically-derived oxidative stress by inhibiting the cycling of glutathione and thioredoxin, which induced insulin resistance as measured by impaired insulin-stimulated 2-deoxyglucose uptake...
January 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29375041/chronic-orexin-a-hypocretin-1-treatment-of-type-2-diabetic-rats-improves-glucose-control-and-beta-cell-functions
#11
P Kaczmarek, M Skrzypski, E Pruszynska-Oszmalek, M Sassek, P A Kolodziejski, M Billert, D Szczepankiewicz, T Wojciechowicz, P Maechler, K W Nowak, M Z Strowski
Orexin regulates food intake and energy expenditure. Here, we test the ability of orexin-A (OXA, hypocretin-1) at improving metabolic control in type 2 diabetic animals and elaborate potential mechanisms of action. Rats with experimentally induced type 2 diabetes by a combination of streptozotocin injection and high-fat diet feeding were chronically infused with OXA. In vitro experiments were conducted on isolated pancreatic islets, primary adipocytes and insulin secreting INS-1E cells. OXA improved glucose control, enhanced insulin sensitivity and attenuated pancreatic β-cell loss in type 2 diabetic rats...
October 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29323267/scaffold-free-generation-of-uniform-adipose-spheroids-for-metabolism-research-and-drug-discovery
#12
Aloysius J Klingelhutz, Francoise A Gourronc, Anna Chaly, David A Wadkins, Anthony J Burand, Kathleen R Markan, Sharon O Idiga, Meng Wu, Matthew J Potthoff, James A Ankrum
Adipose tissue dysfunction is critical to the development of type II diabetes and other metabolic diseases. While monolayer cell culture has been useful for studying fat biology, 2D culture often does not reflect the complexity of fat tissue. Animal models are also problematic in that they are expensive, time consuming, and may not completely recapitulate human biology because of species variation. To address these problems, we have developed a scaffold-free method to generate 3D adipose spheroids from primary or immortal human or mouse pre-adipocytes...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317436/the-diabetes-gene-and-wnt-pathway-effector-tcf7l2-regulates-adipocyte-development-and-function
#13
Xi Chen, Iriscilla Ayala, Chris Shannon, Marcel Fourcaudot, Nikhil K Acharya, Christopher P Jenkinson, Sami Heikkinen, Luke Norton
The gene encoding for transcription factor 7-like 2 ( TCF7L2 ) is the strongest type 2 diabetes mellitus (T2DM) candidate gene discovered to date. The TCF7L2 protein is a key transcriptional effector of the Wnt/β-catenin signaling pathway, which is an important developmental pathway that negatively regulates adipogenesis. However, the precise role that TCF7L2 plays in the development and function of adipocytes remains largely unknown. Using a combination of in vitro approaches, we first show that TCF7L2 protein is increased during adipogenesis in 3T3-L1 cells and primary adipocyte stem cells and that TCF7L2 expression is required for the regulation of Wnt signaling during adipogenesis...
April 2018: Diabetes
https://www.readbyqxmd.com/read/29283422/hyperglycemia-augments-the-adipogenic-transdifferentiation-potential-of-tenocytes-and-is-alleviated-by-cyclic-mechanical-stretch
#14
Yu-Fu Wu, Yu-Ting Huang, Hsing-Kuo Wang, Chung-Chen Jane Yao, Jui-Sheng Sun, Yuan-Hung Chao
Diabetes mellitus is associated with damage to tendons, which may result from cellular dysfunction in response to a hyperglycemic environment. Tenocytes express diminished levels of tendon-associated genes under hyperglycemic conditions. In contrast, mechanical stretch enhances tenogenic differentiation. However, whether hyperglycemia increases the non-tenogenic differentiation potential of tenocytes and whether this can be mitigated by mechanical stretch remains elusive. We explored the in vitro effects of high glucose and mechanical stretch on rat primary tenocytes...
December 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29237539/cdkn2a-deficiency-promotes-adipose-tissue-browning
#15
Nabil Rabhi, Sarah Anissa Hannou, Xavier Gromada, Elisabet Salas, Xi Yao, Frédérik Oger, Charlène Carney, Isabel C Lopez-Mejia, Emmanuelle Durand, Iandry Rabearivelo, Amélie Bonnefond, Emilie Caron, Lluis Fajas, Christian Dani, Philippe Froguel, Jean-Sébastien Annicotte
OBJECTIVES: Genome-wide association studies have reported that DNA polymorphisms at the CDKN2A locus modulate fasting glucose in human and contribute to type 2 diabetes (T2D) risk. Yet the causal relationship between this gene and defective energy homeostasis remains elusive. Here we sought to understand the contribution of Cdkn2a to metabolic homeostasis. METHODS: We first analyzed glucose and energy homeostasis from Cdkn2a-deficient mice subjected to normal or high fat diets...
February 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29167318/trail-reduces-impaired-glucose-tolerance-and-nafld-in-the-high-fat-diet-fed-mouse
#16
Stella Bernardi, Barbara Toffoli, Veronica Tisato, Fleur Bossi, Stefania Biffi, Andrea Lorenzon, Giorgio Zauli, Paola Secchiero, Bruno Fabris
Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis inducing ligand) may have an important role in the treatment of type 2 diabetes. It has been shown that TRAIL deficiency worsens diabetes and that TRAIL delivery, when it is given before disease onset, slows down its development. The present study aimed at evaluating whether TRAIL had the potential not only to prevent, but also to treat type 2 diabetes. Thirty male C57BL/6J mice were randomized to a standard or a high-fat diet (HFD)...
January 16, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29155147/selective-and-membrane-permeable-small-molecule-inhibitors-of-nicotinamide-n-methyltransferase-reverse-high-fat-diet-induced-obesity-in-mice
#17
Harshini Neelakantan, Virginia Vance, Michael D Wetzel, Hua-Yu Leo Wang, Stanton F McHardy, Celeste C Finnerty, Jonathan D Hommel, Stanley J Watowich
There is a critical need for new mechanism-of-action drugs that reduce the burden of obesity and associated chronic metabolic comorbidities. A potentially novel target to treat obesity and type 2 diabetes is nicotinamide-N-methyltransferase (NNMT), a cytosolic enzyme with newly identified roles in cellular metabolism and energy homeostasis. To validate NNMT as an anti-obesity drug target, we investigated the permeability, selectivity, mechanistic, and physiological properties of a series of small molecule NNMT inhibitors...
January 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29097199/trpv4-is-involved-in-irisin-induced-endothelium-dependent-vasodilation
#18
Li Ye, Mengnan Xu, Min Hu, Hai Zhang, Xianming Tan, Qing Li, Bing Shen, Junhao Huang
Irisin, an exercise-induced myokine, induces conversion of white into brown adipocytes, promoting mitochondrial biogenesis and energy expenditure. Irisin has a vascular protective effect on endothelial function in animals, including humans. Defects in irisin signaling pathways result in endothelial dysfunction in obesity and diabetes. However, the mechanisms underlying the effects of irisin on endothelial function have not been elucidated. Transient receptor potential vanilloid subtype 4 (TRPV4) channels are one of the most important Ca2+ -permeable cation channels in vascular endothelial cells...
January 1, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29046921/pioglitazone-reduces-cold-induced-brown-fat-glucose-uptake-despite-induction-of-browning-in-cultured-human-adipocytes-a-randomised-controlled-trial-in-humans
#19
Rebecca K C Loh, Melissa F Formosa, Nina Eikelis, David A Bertovic, Mitchell J Anderson, Shane A Barwood, Shane Nanayakkara, Neale D Cohen, Andre La Gerche, Anne T Reutens, Kenneth S Yap, Thomas W Barber, Gavin W Lambert, Martin H Cherk, Stephen J Duffy, Bronwyn A Kingwell, Andrew L Carey
AIMS/HYPOTHESIS: Increasing brown adipose tissue (BAT) activity is a possible therapeutic strategy to increase energy expenditure and glucose and lipid clearance to ameliorate obesity and associated comorbidities. The thiazolidinedione (TZD) class of glucose-lowering drugs increase BAT browning in preclinical experimental models but whether these actions extend to humans in vivo is unknown. The aim of this study was to determine the effect of pioglitazone treatment on adipocyte browning and adaptive thermogenesis in humans...
January 2018: Diabetologia
https://www.readbyqxmd.com/read/29031721/cdkal1-a-type-2-diabetes-susceptibility-gene-regulates-mitochondrial-function-in-adipose-tissue
#20
Colin J Palmer, Raphael J Bruckner, Joao A Paulo, Lawrence Kazak, Jonathan Z Long, Amir I Mina, Zhaoming Deng, Katherine B LeClair, Jessica A Hall, Shangyu Hong, Peter-James H Zushin, Kyle L Smith, Steven P Gygi, Susan Hagen, David E Cohen, Alexander S Banks
OBJECTIVES: Understanding how loci identified by genome wide association studies (GWAS) contribute to pathogenesis requires new mechanistic insights. Variants within CDKAL1 are strongly linked to an increased risk of developing type 2 diabetes and obesity. Investigations in mouse models have focused on the function of Cdkal1 as a tRNALys modifier and downstream effects of Cdkal1 loss on pro-insulin translational fidelity in pancreatic β-cells. However, Cdkal1 is broadly expressed in other metabolically relevant tissues, including adipose tissue...
October 2017: Molecular Metabolism
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