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fatty acids and insulin-secreting cells

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https://www.readbyqxmd.com/read/28431377/metabolic-regulation-and-the-anti-obesity-perspectives-of-human-brown-fat
#1
REVIEW
Camilla Scheele, Søren Nielsen
Activation of brown adipose tissue (BAT) in adult humans increase glucose and fatty acid clearance as well as resting metabolic rate, whereas a prolonged elevation of BAT activity improves insulin sensitivity. However, substantial reductions in body weight following BAT activation has not yet been shown in humans. This observation raise the possibility for feedback mechanisms in adult humans in terms of a brown fat-brain crosstalk, possibly mediated by batokines, factors produced by and secreted from brown fat...
April 11, 2017: Redox Biology
https://www.readbyqxmd.com/read/28431319/response-of-plasma-glucagon-like-peptide-2-to-feeding-pattern-and-intraruminal-administration-of-volatile-fatty-acids-in-sheep
#2
M Elsabagh, Y Inabu, T Obitsu, T Sugino
Glucagon-like peptide-2 (GLP-2), a gut peptide secreted by enteroendocrine L cells, has recently been identified as a key regulator of intestinal growth and absorptive function in ruminants. However, reports on GLP-2 secretion are few, and more information regarding its secretion dynamics is needed. In this study, two experiments were conducted to elucidate the daily rhythm of GLP-2 secretion in response to feeding regimen and to investigate the effect of volatile fatty acids (VFA) on GLP-2 release in sheep...
March 11, 2017: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/28377873/molecular-phenotyping-of-multiple-mouse-strains-under-metabolic-challenge-uncovers-a-role-for-elovl2-in-glucose-induced-insulin-secretion
#3
Céline Cruciani-Guglielmacci, Lara Bellini, Jessica Denom, Masaya Oshima, Neïké Fernandez, Priscilla Normandie-Levi, Xavier P Berney, Nadim Kassis, Claude Rouch, Julien Dairou, Tracy Gorman, David M Smith, Anna Marley, Robin Liechti, Dmitry Kuznetsov, Leonore Wigger, Frédéric Burdet, Anne-Laure Lefèvre, Isabelle Wehrle, Ingo Uphues, Tobias Hildebrandt, Werner Rust, Catherine Bernard, Alain Ktorza, Guy A Rutter, Raphael Scharfmann, Ioannis Xenarios, Hervé Le Stunff, Bernard Thorens, Christophe Magnan, Mark Ibberson
OBJECTIVE: In type 2 diabetes (T2D), pancreatic β cells become progressively dysfunctional, leading to a decline in insulin secretion over time. In this study, we aimed to identify key genes involved in pancreatic beta cell dysfunction by analyzing multiple mouse strains in parallel under metabolic stress. METHODS: Male mice from six commonly used non-diabetic mouse strains were fed a high fat or regular chow diet for three months. Pancreatic islets were extracted and phenotypic measurements were recorded at 2 days, 10 days, 30 days, and 90 days to assess diabetes progression...
April 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28352665/insulin-s-direct-hepatic-effect-explains-the-inhibition-of-glucose-production-caused-by-insulin-secretion
#4
Dale S Edgerton, Guillaume Kraft, Marta Smith, Ben Farmer, Phillip E Williams, Katie C Coate, Richard L Printz, Richard M O'Brien, Alan D Cherrington
Insulin can inhibit hepatic glucose production (HGP) by acting directly on the liver as well as indirectly through effects on adipose tissue, pancreas, and brain. While insulin's indirect effects are indisputable, their physiologic role in the suppression of HGP seen in response to increased insulin secretion is not clear. Likewise, the mechanisms by which insulin suppresses lipolysis and pancreatic α cell secretion under physiologic circumstances are also debated. In this study, insulin was infused into the hepatic portal vein to mimic increased insulin secretion, and insulin's indirect liver effects were blocked either individually or collectively...
March 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28338397/clove-and-its-active-compound-attenuate-free-fatty-acid-mediated-insulin-resistance-in-skeletal-muscle-cells-and-in-mice
#5
Safina Ghaffar, Shabbir Khan Afridi, Meha Fatima Aftab, Munazza Murtaza, Rahman M Hafizur, Sara Sara, Sabira Begum, Rizwana Sanaullah Waraich
Several reports indicate anti-hyperglycemic effects of Syzygium aromaticum. In the present study, we report for the first time that clove extract (SAM) and its compound nigricin (NGC) decreases free fatty acid-mediated insulin resistance in mouse myoblasts. In addition, NGC was able to diminish insulin resistance in a diabetic mouse model. We observed that SAM and its compound NGC exhibited significant antioxidant activity in murine skeletal muscle cells. They also modulated stress signaling by reducing p38 MAP kinase phosphorylation...
April 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28303004/serum-fabp5-concentration-is-a-potential-biomarker-for-residual-risk-of-atherosclerosis-in-relation-to-cholesterol-efflux-from-macrophages
#6
Masato Furuhashi, Masatsune Ogura, Megumi Matsumoto, Satoshi Yuda, Atsuko Muranaka, Mina Kawamukai, Akina Omori, Marenao Tanaka, Norihito Moniwa, Hirofumi Ohnishi, Shigeyuki Saitoh, Mariko Harada-Shiba, Kazuaki Shimamoto, Tetsuji Miura
Cholesterol efflux capacity (CEC) from macrophages, the first step in the reverse cholesterol transport pathway, is inversely associated with residual risk for atherosclerotic cardiovascular disease. Fatty acid-binding protein 4 (FABP4) and FABP5 are expressed in both adipocytes and macrophages and play significant roles in the development of insulin resistance and atherosclerosis. Both FABP4 and FABP5 are secreted from cells, and their circulating levels are associated with insulin resistance and atherosclerosis...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28277660/discovery-of-potent-and-orally-bioavailable-gpr40-full-agonists-bearing-thiophen-2-ylpropanoic-acid-scaffold
#7
He Li, Qi Huang, Cheng Chen, Bin Xu, He-Yao Wang, Ya-Qiu Long
The free fatty acid receptor GPR40 is predominantly expressed in pancreatic β-cells and enhances insulin secretion in a glucose dependent manner. Therefore, GPR40 agonists are possible novel insulin secretagogues with reduced or no risk of hypoglycemia for the treatment of type 2 diabetes mellitus (T2DM). Chemically and structurally diverse GPR40 agonists with high safety are pursued for the clinical development of GPR40-based pharmacotherapeutics. Herein we report our design and discovery of a new chemotype of GPR40 agonists free of the typical phenylpropanoic acid scaffold...
April 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28240264/overexpressing-the-novel-autocrine-endocrine-adipokine-wisp2-induces-hyperplasia-of-the-heart-white-and-brown-adipose-tissues-and-prevents-insulin-resistance
#8
John R Grünberg, Jenny M Hoffmann, Shahram Hedjazifar, Annika Nerstedt, Lachmi Jenndahl, Johannes Elvin, John Castellot, Lan Wei, Sofia Movérare-Skrtic, Claes Ohlsson, Louise Mannerås Holm, Fredrik Bäckhed, Ismail Syed, Fatima Bosch, Alan Saghatelian, Barbara B Kahn, Ann Hammarstedt, Ulf Smith
WISP2 is a novel adipokine, most highly expressed in the adipose tissue and primarily in undifferentiated mesenchymal cells. As a secreted protein, it is an autocrine/paracrine activator of canonical WNT signaling and, as an intracellular protein, it helps to maintain precursor cells undifferentiated. To examine effects of increased WISP2 in vivo, we generated an aP2-WISP2 transgenic (Tg) mouse. These mice had increased serum levels of WISP2, increased lean body mass and whole body energy expenditure, hyperplastic brown/white adipose tissues and larger hyperplastic hearts...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28236846/the-prevention-of-benign-prostatic-hyperplasia-bph
#9
W G Roper
Barry Marshall and Robin Warren were the first to show that the chronic diseases (gastric ulcer and chronic gastritis) were caused by an infection (Helicobacter pylori). The chronic disease benign prostatic hyperplasia belongs to the same ilk, except that the infection process is much more subtle and complex. The enzyme Phospholipase D (PLD) which is attached to the outer membrane of Escherichia coli (E. coli) has now been almost completely proven to be the basic cause of BPH. The evidence for this process is now extremely strong and compelling...
March 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28196858/the-2016-walter-b-cannon-lecture-deconstructing-metabolic-inflammation-using-cellular-systems
#10
Kenny L Chan, Parastoo Boroumand, Marciane Milanski, Nicolas J Pillon, Philip J Bilan, Amira Klip
Over the past years we have embarked in a systematic analysis of the effect of obesity or fatty acids on circulating monocytes, microvascular endothelial cells, macrophages and skeletal muscle cells. Using cell culture strategies, we have deconstructed complex physiological systems, then reconstructed 'partial equations' to better understand cell-to-cell communication. Through these approaches we identified that in high saturated fat environments, cell-autonomous pro-inflammatory pathways are activated in monocytes and endothelial cells, promoting monocyte adhesion and transmigration...
February 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28193492/characterization-of-acyl-coa-synthetase-isoforms-in-pancreatic-beta-cells-gene-silencing-shows-participation-of-acsl3-and-acsl4-in-insulin-secretion
#11
Israr-Ul H Ansari, Melissa J Longacre, Scott W Stoker, Mindy A Kendrick, Lucas M O'Neill, Laura J Zitur, Luis A Fernandez, James M Ntambi, Michael J MacDonald
Long-chain acyl-CoA synthetases (ACSLs) convert fatty acids to fatty acyl-CoAs to regulate various physiologic processes. We characterized the ACSL isoforms in a cell line of homogeneous rat beta cells (INS-1 832/13 cells) and human pancreatic islets. ACSL4 and ACSL3 proteins were present in the beta cells and human and rat pancreatic islets and concentrated in insulin secretory granules and less in mitochondria and negligible in other intracellular organelles. ACSL1 and ACSL6 proteins were not seen in INS-1 832/13 cells or pancreatic islets...
March 15, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28154332/a-new-pain-regulatory-system-via-the-brain-long-chain-fatty-acid-receptor-gpr40-ffa1-signal
#12
Kazuo Nakamoto
 An increasingly large number of pharmacological and physiological works on fatty acids have shown that the functional properties of fatty acids are regulated by the amount of individual fatty acid intake and the distribution of fatty acids among organs. Recently, it has been determined that G-protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFA1) is activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). GPR40/FFA1 is mainly expressed in the β cell of the pancreas, spinal cord and brain...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28139377/cpt1a-methylation-is-associated-with-plasma-adiponectin
#13
S Aslibekyan, A N Do, H Xu, S Li, M R Irvin, D Zhi, H K Tiwari, D M Absher, A R Shuldiner, T Zhang, W Chen, K Tanner, C Hong, B D Mitchell, G Berenson, D K Arnett
BACKGROUND AND AIMS: Adiponectin, an adipose-secreted protein that has been linked to insulin sensitivity, plasma lipids, and inflammatory patterns, is an established biomarker for metabolic health. Despite clinical relevance and high heritability, the determinants of plasma adiponectin levels remain poorly understood. METHODS AND RESULTS: We conducted the first epigenome-wide cross-sectional study of adiponectin levels using methylation data on 368,051 cytosine-phosphate-guanine (CpG) sites in CD4+ T-cells from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n = 991)...
March 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28130074/loss-of-ucp2-impairs-cold-induced-non-shivering-thermogenesis-by-promoting-a-shift-toward-glucose-utilization-in-brown-adipose-tissue
#14
Alexandre Caron, Sébastien M Labbé, Sophie Carter, Marie-Claude Roy, Roger Lecomte, Daniel Ricquier, Frédéric Picard, Denis Richard
Uncoupling protein 2 (UCP2) was discovered in 1997 and classified as an uncoupling protein largely based on its homology of sequence with UCP1. Since its discovery, the uncoupling function of UCP2 has been questioned and there is yet no consensus on the true function of this protein. UCP2 was first proposed to be a reactive oxygen species (ROS) regulator and an insulin secretion modulator. More recently, it was demonstrated as a regulator of the mitochondrial fatty acid oxidation, which prompted us to investigate its role in the metabolic and thermogenic functions of brown adipose tissue...
March 2017: Biochimie
https://www.readbyqxmd.com/read/28115493/esculentin-2cha-1-30-and-its-analogues-stability-and-mechanisms-of-insulinotropic-action
#15
Srividya Vasu, Mary K McGahon, R Charlotte Moffett, Tim M Curtis, J Michael Conlon, Yasser H A Abdel-Wahab, Peter R Flatt
The insulin-releasing effects, cellular mechanisms of action and anti-hyperglycaemic activity of 10 analogues of esculentin-2CHa lacking the cyclic C-terminal domain (CKISKQC) were evaluated. Analogues of the truncated peptide, esculentin-2CHa(1-30), were designed for plasma enzyme resistance and increased biological activity. Effects of those analogues on insulin release, cell membrane integrity, membrane potential, intracellular Ca(2+) and cAMP levels were determined using clonal BRIN-BD11 cells. Their acute effects on glucose tolerance were investigated using NIH Swiss mice...
March 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28078385/glucose-and-fatty-acids-synergistically-and-reversibly-promote-beta-cell-proliferation-in-rats
#16
Valentine S Moullé, Kevin Vivot, Caroline Tremblay, Bader Zarrouki, Julien Ghislain, Vincent Poitout
AIMS/HYPOTHESIS: The mechanisms underlying pancreatic islet mass expansion have attracted considerable interest as potential therapeutic targets to prevent or delay the onset of type 2 diabetes. While several factors promoting beta cell proliferation have been identified, in the context of nutrient excess the roles of glucose or NEFA in relation to insulin resistance remain unclear. Here we tested the hypothesis that glucose and NEFA synergistically and reversibly promote beta cell proliferation in the context of nutrient-induced insulin resistance...
May 2017: Diabetologia
https://www.readbyqxmd.com/read/28069865/interleukin-22-restored-mitochondrial-damage-and-impaired-glucose-stimulated-insulin-secretion-through-down-regulation-of-uncoupling-protein-2-in-ins-1-cells
#17
Minling Hu, Hanxiao Lin, Li Yang, Yanzhen Cheng, Hua Zhang
Defective glucose-stimulated insulin secretion (GSIS) induced by chronic exposure to fatty acids is a hallmark of type 2 diabetes (T2D). Interleukin-22 (IL-22) has been shown to exert beneficial effects on insulin secretion and to protect pancreatic β-cells from stress. Moreover, uncoupling protein-2 (UCP-2) plays a central role in the regulation of GSIS and β-cell dysfunction, whereas the role of UCP-2 in IL-22-enhanced glycemic control under conditions of lipotoxicity remains unclear. In this present study, we investigated the effects of IL-22 on rat insulin-secreting cells (INS-1 cells) and the mechanisms that underlie IL-22 and lipotoxicity-impaired GSIS in vitro...
January 7, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28045398/skeletal-muscle-inflammation-and-insulin-resistance-in-obesity
#18
Huaizhu Wu, Christie M Ballantyne
Obesity is associated with chronic inflammation, which contributes to insulin resistance and type 2 diabetes mellitus. Under normal conditions, skeletal muscle is responsible for the majority of insulin-stimulated whole-body glucose disposal; thus, dysregulation of skeletal muscle metabolism can strongly influence whole-body glucose homeostasis and insulin sensitivity. Increasing evidence suggests that inflammation occurs in skeletal muscle in obesity and is mainly manifested by increased immune cell infiltration and proinflammatory activation in intermyocellular and perimuscular adipose tissue...
January 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28027586/targeting-the-mitochondrial-pyruvate-carrier-attenuates-fibrosis-in-a-mouse-model-of-nonalcoholic-steatohepatitis
#19
Kyle S McCommis, Wesley T Hodges, Elizabeth M Brunt, Ilke Nalbantoglu, William G McDonald, Christopher Holley, Hideji Fujiwara, Jean E Schaffer, Jerry R Colca, Brian N Finck
Diseases of the liver related to metabolic syndrome have emerged as the most common and undertreated hepatic ailments. The cause of nonalcoholic fatty liver disease is the aberrant accumulation of lipid in hepatocytes, though the mechanisms whereby this leads to hepatocyte dysfunction, death, and hepatic fibrosis are still unclear. Insulin-sensitizing thiazolidinediones have shown efficacy in treating nonalcoholic steatohepatitis (NASH), but their widespread use is constrained by dose-limiting side effects thought to be due to activation of the peroxisome proliferator-activated receptor γ...
May 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28018462/a-novel-mutation-of-abcc8-gene-in-a-patient-with-diazoxide-unresponsive-congenital-hyperinsulinism
#20
Ji Sook Park, Hong-Jun Lee, Chan-Hoo Park
Congenital hyperinsulinism (CHI) is a rare condition that can cause irreversible brain damage during the neonatal period owing to the associated hypoglycemia. Hypoglycemia in CHI occurs secondary to the dysregulation of insulin secretion. CHI has been established as a genetic disorder of islet-cell hyperplasia, associated with a mutation of the ABCC8 or KCNJ11 genes, which encode the sulfonylurea receptor 1 and the inward rectifying potassium channel (Kir6.2) subunit of the ATP-sensitive potassium channel, respectively...
November 2016: Korean Journal of Pediatrics
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