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fatty acids and insulin-secreting cells

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https://www.readbyqxmd.com/read/28196858/the-2016-walter-b-cannon-lecture-deconstructing-metabolic-inflammation-using-cellular-systems
#1
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
#2
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...
February 11, 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
#3
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
#4
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)...
November 23, 2016: 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
#5
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
#6
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
#7
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...
January 11, 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
#8
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
#9
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
#10
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 (NAFLD) 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 (PPARγ)...
December 27, 2016: 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
#11
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
https://www.readbyqxmd.com/read/28018292/obesity-an-immunometabolic-perspective
#12
REVIEW
Indrani Ray, Sushil K Mahata, Rajat K De
Obesity, characterized by chronic activation of inflammatory pathways, is a critical factor contributing to insulin resistance (IR) and type 2 diabetes (T2D). Free fatty acids (FFAs) are increased in obesity and are implicated as proximate causes of IR and induction of inflammatory signaling in adipose, liver, muscle, and pancreas. Cells of the innate immune system produce cytokines, and other factors that affect insulin signaling and result in the development of IR. In the lean state, adipose tissue is populated by adipose tissue macrophage of the anti-inflammatory M2 type (ATM2) and natural killer (NK) cells; this maintains the insulin-sensitive phenotype because ATM2 cells secrete IL10...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28002466/assessment-of-the-role-of-metabolic-determinants-on-the-relationship-between-insulin-sensitivity-and-secretion
#13
Jose E Galgani, Carmen Gómez, Maria L Mizgier, Juan Gutierrez, Jose L Santos, Pablo Olmos, Andrea Mari
BACKGROUND: Insulin secretion correlates inversely with insulin sensitivity, which may suggest the existence of a crosstalk between peripheral organs and pancreas. Such interaction might be mediated through glucose oxidation that may drive the release of circulating factors with action on insulin secretion. AIM: To evaluate the association between whole-body carbohydrate oxidation and circulating factors with insulin secretion to consecutive oral glucose loading in non-diabetic individuals...
2016: PloS One
https://www.readbyqxmd.com/read/27994752/identification-of-an-orally-efficacious-gpr40-ffar1-receptor-agonist
#14
Sameer Agarwal, Santosh Sasane, Prashant Deshmukh, Bhadresh Rami, Debdutta Bandyopadhyay, Poonam Giri, Suresh Giri, Mukul Jain, Ranjit C Desai
GPR40/FFAR1 is a G protein-coupled receptor predominantly expressed in pancreatic β-cells and activated by long-chain free fatty acids, mediating enhancement of glucose-stimulated insulin secretion. A novel series of substituted 3-(4-aryloxyaryl)propanoic acid derivatives were prepared and evaluated for their activities as GPR40 agonists, leading to the identification of compound 5, which is highly potent in in vitro assays and exhibits robust glucose lowering effects during an oral glucose tolerance test in nSTZ Wistar rat model of diabetes (ED50 = 0...
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27990542/3d-templated-fully-automated-microfluidic-input-output-multiplexer-for-endocrine-tissue-culture-and-secretion-sampling
#15
Xiangpeng Li, Jessica C Brooks, Juan Hu, Katarena I Ford, Christopher J Easley
A fully automated, 16-channel microfluidic input/output multiplexer (μMUX) has been developed for interfacing to primary cells and to improve understanding of the dynamics of endocrine tissue function. The device utilizes pressure driven push-up valves for precise manipulation of nutrient input and hormone output dynamics, allowing time resolved interrogation of the cells. The ability to alternate any of the 16 channels from input to output, and vice versa, provides for high experimental flexibility without the need to alter microchannel designs...
January 17, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/27964715/differential-effects-of-palmitoleic-acid-on-human-lymphocyte-proliferation-and-function
#16
M E P Passos, H H O Alves, C M Momesso, F G Faria, G Murata, M F Cury-Boaventura, E Hatanaka, S Massao-Hirabara, R Gorjão
BACKGROUND: Palmitoleic acid (PA) is a n-7 monounsaturated fatty acid (MUFA) secreted by adipose tissue and related to decreased insulin resistance in peripheral tissues. Evidences have been shown that PA also decreased proinflammatory cytokine expression in cultured macrophages. Although studies have shown that other fatty acids (FAs) modulate several lymphocyte functions, the specific effect of PA on these cells is unknown. The aim of the present study was to evaluate the possible influence of PA on activation and differentiation of human lymphocytes in comparison to oleic acid (OA)...
December 13, 2016: Lipids in Health and Disease
https://www.readbyqxmd.com/read/27959892/ffa2-contribution-to-gestational-glucose-tolerance-is-not-disrupted-by-antibiotics
#17
Miles Fuller, Xiaoran Li, Robert Fisch, Moneb Bughara, Barton Wicksteed, Petia Kovatcheva-Datchary, Brian T Layden
During the insulin resistant phase of pregnancy, the mRNA expression of free fatty acid 2 receptor (Ffar2) is upregulated and as we recently reported, this receptor contributes to insulin secretion and pancreatic beta cell mass expansion in order to maintain normal glucose homeostasis during pregnancy. As impaired gestational glucose levels can affect metabolic health of offspring, we aimed to explore the role of maternal Ffar2 expression during pregnancy on the metabolic health of offspring and also the effects of antibiotics, which have been shown to disrupt gut microbiota fermentative activity (the source of the FFA2 ligands) on gestational glucose homeostasis...
2016: PloS One
https://www.readbyqxmd.com/read/27942596/development-of-an-in-vitro-human-liver-system-for-interrogating-nonalcoholic-steatohepatitis
#18
Ryan E Feaver, Banumathi K Cole, Mark J Lawson, Stephen A Hoang, Svetlana Marukian, Brett R Blackman, Robert A Figler, Arun J Sanyal, Brian R Wamhoff, Ajit Dash
A barrier to drug development for nonalcoholic steatohepatitis (NASH) is the absence of translational preclinical human-relevant systems. An in vitro liver model was engineered to incorporate hepatic sinusoidal flow, transport, and lipotoxic stress risk factors (glucose, insulin, free fatty acids) with cocultured primary human hepatocytes, hepatic stellate cells (HSCs), and macrophages. Transcriptomic, lipidomic, and functional endpoints were evaluated and compared with clinical data from NASH patient biopsies...
December 8, 2016: JCI Insight
https://www.readbyqxmd.com/read/27927723/coordinated-activation-of-mitochondrial-respiration-and-exocytosis-mediated-by-pkc-signaling-in-pancreatic-%C3%AE-cells
#19
Jaime Santo-Domingo, Isabelle Chareyron, Loïc Dayon, Antonio Núñez Galindo, Ornella Cominetti, María Pilar Giner Giménez, Umberto De Marchi, Carles Canto, Martin Kussmann, Andreas Wiederkehr
Mitochondria play a central role in pancreatic β-cell nutrient sensing by coupling their metabolism to plasma membrane excitability and insulin granule exocytosis. Whether non-nutrient secretagogues stimulate mitochondria as part of the molecular mechanism to promote insulin secretion is not known. Here, we show that PKC signaling, which is employed by many non-nutrient secretagogues, augments mitochondrial respiration in INS-1E (rat insulinoma cell line clone 1E) and human pancreatic β-cells. The phorbol ester, phorbol 12-myristate 13-acetate, accelerates mitochondrial respiration at both resting and stimulatory glucose concentrations...
December 7, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27914538/adaptive-response-of-rat-pancreatic-%C3%AE-cells-to-insulin-resistance-induced-by-monocrotophos-biochemical-evidence
#20
Raju Nagaraju, Padmanabhan Sharda Rajini
Our previous findings clearly suggested the role of duration of exposure to monocrotophos (MCP) in the development of insulin resistance. Rats exposed chronically to MCP developed insulin resistance with hyperinsulinemia without overt diabetes. In continuation of this vital observation, we sought to delineate the biochemical mechanisms that mediate heightened pancreatic β-cell response in the wake of MCP-induced insulin resistance in rats. Adult rats were orally administered (0.9 and 1.8mg/kgb.w/d) MCP for 180days...
November 2016: Pesticide Biochemistry and Physiology
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