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fatty acids and insulin-secreting cells

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https://www.readbyqxmd.com/read/28933059/function-and-dysfunction-of-adipose-tissue
#1
Paulo Matafome, Raquel Seiça
Adipose tissue is an endocrine organ which is responsible for postprandial uptake of glucose and fatty acids, consequently producing a broad range of adipokines controlling several physiological functions like appetite, insulin sensitivity and secretion, immunity, coagulation, and vascular tone, among others. Many aspects of adipose tissue pathophysiology in metabolic diseases have been described in the last years. Recent data suggest two main factors for adipose tissue dysfunction: accumulation of nonesterified fatty acids and their secondary products and hypoxia...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28903937/ectopic-fatty-acid-binding-protein-4-expression-in-the-vascular-endothelium-is-involved-in-neointima-formation-after-vascular-injury
#2
Takahiro Fuseya, Masato Furuhashi, Megumi Matsumoto, Yuki Watanabe, Kyoko Hoshina, Tomohiro Mita, Shutaro Ishimura, Marenao Tanaka, Tetsuji Miura
BACKGROUND: Fatty acid-binding protein 4 (FABP4) is expressed in adipocytes, macrophages, and endothelial cells of capillaries but not arteries. FABP4 is secreted from adipocytes in association with lipolysis, and an elevated circulating FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the link between FABP4 and endovascular injury. We investigated the involvement of ectopic FABP4 expression in endothelial cells in neointima hyperplasia after vascular injury...
September 13, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28868828/in-vitro-effect-of-fatty-acids-identified-in-the-plasma-of-obese-adolescents-on-the-function-of-pancreatic-%C3%AE-cells
#3
Claudia Velasquez, Juan Sebastian Vasquez, Norman Balcazar
BACKGROUND: The increase in circulating free fatty acid (FFA) levels is a major factor that induces malfunction in pancreatic β-cells. We evaluated the effect of FFAs reconstituted according to the profile of circulating fatty acids found in obese adolescents on the viability and function of the murine insulinoma cell line (mouse insulinoma [MIN6]). METHODS: From fatty acids obtained commercially, plasma-FFA profiles of three different youth populations were reconstituted: obese with metabolic syndrome; obese without metabolic syndrome; and normal weight without metabolic syndrome...
August 2017: Diabetes & Metabolism Journal
https://www.readbyqxmd.com/read/28862812/performance-of-individually-measured-vs-population-based-c-peptide-kinetics-to-assess-%C3%AE-cell-function-in-presence-and-absence-of-acute-insulin-resistance
#4
Ron T Varghese, Chiara Dalla Man, Marcello C Laurenti, Francesca Piccinini, Anu Sharma, Meera Shah, Kent R Bailey, Robert A Rizza, Claudio Cobelli, Adrian Vella
AIMS: Standardized, population-based kinetics of C-peptide distribution and clearance are used to estimate insulin secretion from plasma C-peptide concentrations without direct measurement of C-peptide kinetics. We then compared the performance of population-based kinetics to directly measured C-peptide kinetics when used to calculate β-cell responsivity indices. To ensure that population-based kinetics apply to all conditions where β-cell function is measured, subjects were studied in the presence and absence of acute insulin resistance...
September 1, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28828705/glucotoxicity-promotes-aberrant-activation-and-mislocalization-of-ras-related-c3-botulinum-toxin-substrate-1-rac1-and-metabolic-dysfunction-in-pancreatic-islet-%C3%AE-cells-reversal-of-such-metabolic-defects-by-metformin
#5
Sartaj Baidwan, Anil Chekuri, DiAnna L Hynds, Anjaneyulu Kowluru
Emerging evidence suggests that long-term exposure of insulin-secreting pancreatic β-cells to hyperglycemic (HG; glucotoxic) conditions promotes oxidative stress, which, in turn, leads to stress kinase activation, mitochondrial dysfunction, loss of nuclear structure and integrity and cell apoptosis. Original observations from our laboratory have proposed that Rac1 plays a key regulatory role in the generation of oxidative stress and downstream signaling events culminating in the onset of dysfunction of pancreatic β-cells under the duress of metabolic stress...
August 21, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28827783/ccdc3-a-new-p63-target-involved-in-regulation-of-liver-lipid-metabolism
#6
Wenjuan Liao, Hongbing Liu, Yiwei Zhang, Ji Hoon Jung, Jiaxiang Chen, Xiaohua Su, Yeong C Kim, Elsa R Flores, San Ming Wang, Malwina Czarny-Ratajczak, Wen Li, Shelya X Zeng, Hua Lu
TAp63, a member of the p53 family, has been shown to regulate energy metabolism. Here, we report coiled coil domain-containing 3 (CCDC3) as a new TAp63 target. TAp63, but not ΔNp63, p53 or p73, upregulates CCDC3 expression by directly binding to its enhancer region. The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity, but induced by metformin, an anti-diabetic drug that activates p63...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28826615/glycerol-3-phosphate-phosphatase-pgp-role-in-intermediate-metabolism-and-target-for-cardiometabolic-diseases
#7
REVIEW
Elite Possik, S R Murthy Madiraju, Marc Prentki
Metabolic diseases, including obesity, type 2 diabetes, and metabolic syndrome arise because of disturbances in glucose and fat metabolism, which impact associated physiological events such as insulin secretion and action, fat storage and oxidation. Even though, decades of research has contributed to our current understanding of the components involved in glucose and fat metabolism and their regulation, that led to the development of many therapeutics, there are still many unanswered questions. Glycerol-3-phosphate (Gro3P), which is formed during glycolysis, is at the intersection of glucose and fat metabolism, and the availability of this metabolite can regulate energy and intermediary metabolism in mammalian cells...
August 4, 2017: Biochimie
https://www.readbyqxmd.com/read/28805970/a-novel-free-fatty-acid-receptor-1-gpr40-ffar1-agonist-mr1704-enhances-glucose-dependent-insulin-secretion-and-improves-glucose-homeostasis-in-rats
#8
Naoto Tsuda, Atsuko Kawaji, Toshihiro Sato, Mitsuhiro Takagi, Chika Higashi, Yutaka Kato, Kumiko Ogawa, Hiroyasu Naba, Munetaka Ohkouchi, Masaki Nakamura, Yoshitaka Hosaka, Junichi Sakaki
Activation of G protein-coupled receptor 40/Free fatty acid receptor 1 (GPR40/FFAR1), which is highly expressed in pancreatic β cells, is considered an important pharmacologic target for the treatment of type 2 diabetes mellitus. The aim of this study was to determine the effect of MR1704, a novel GPR40/FFAR1 agonist, on glucose homeostasis in rats. MR1704 is a highly potent and selective, orally bioavailable agonist with similar in vitro potencies among humans, mice, and rats. Treatment of rat islets with MR1704 increased glucose-dependent insulin secretion...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28797566/palmitate-induced-fetuin-a-secretion-from-pancreatic-%C3%AE-cells-adversely-affects-its-function-and-elicits-inflammation
#9
Alpana Mukhuty, Chandrani Fouzder, Sandip Mukherjee, Chandan Malick, Satinath Mukhopadhyay, Samir Bhattacharya, Rakesh Kundu
Islets of type 2 diabetes patients display inflammation, elevated levels of cytokines and macrophages. The master regulator of inflammation in the islets is free fatty acids (FFA). It has already been reported that FFA and TLR4 stimulation induces pro-inflammatory factors in the islets. In this report we demonstrate that excess lipid triggers Fetuin-A (FetA) secretion from the pancreatic β-cells. Palmitate treatment to MIN6 cells showed significantly elevated FetA levels in respect to their controls. Fatty acid induces the FetA gene and protein expression in the pancreatic β-cells via TLR4 and over-expression of NF-κB...
August 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28753206/trpm2-mediated-rise-in-mitochondrial-zn-2-promotes-palmitate-induced-mitochondrial-fission-and-pancreatic-%C3%AE-cell-death-in-rodents
#10
Fangfang Li, Tim S Munsey, Asipu Sivaprasadarao
Rise in plasma free fatty acids (FFAs) represents a major risk factor for obesity-induced type 2 diabetes. Saturated FFAs cause a progressive decline in insulin secretion by promoting pancreatic β-cell death through increased production of reactive oxygen species (ROS). Recent studies have demonstrated that palmitate (a C16-FFA)-induced rise in ROS causes β-cell death by triggering mitochondrial fragmentation, but the underlying mechanisms are unclear. Using the INS1-832/13 β-cell line, here we demonstrate that palmitate generates the ROS required for mitochondrial fission by activating NOX (NADPH oxidase)-2...
July 28, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28751218/brain-lipoprotein-lipase-as-a-regulator-of-energy-balance
#11
Céline Cruciani-Guglielmacci, Christophe Magnan
The central nervous system is an essential actor in the control of the energy balance. Indeed, many signals of nervous (vagal afferent for example) or circulating (hormone, nutrients) origin converge towards the brain to inform it permanently of the energetic status of the organism. In turn, the brain sends information to the periphery (sympathetic vagal balance, thyroid or corticotropic axis) which allows a fine regulation of the energy fluxes by acting on the hepatic glucose production, the secretion of the pancreatic hormones (glucagon, insulin) or food behavior...
July 24, 2017: Biochimie
https://www.readbyqxmd.com/read/28751022/er-resident-antioxidative-gpx7-and-gpx8-enzyme-isoforms-protect-insulin-secreting-ins-1e-%C3%AE-cells-against-lipotoxicity-by-improving-the-er-antioxidative-capacity
#12
Ilir Mehmeti, Stephan Lortz, Edward Avezov, Anne Jörns, Sigurd Lenzen
Increased circulating levels of saturated fatty acids (FFAs) and glucose are considered to be major mediators of β-cell dysfunction and death in T2DM. Although it has been proposed that endoplasmic reticulum (ER) and oxidative stress play a crucial role in gluco/lipotoxicity, their interplay and relative contribution to β-cell dysfunction and apoptosis has not been fully elucidated. In addition it is still unclear how palmitate - the physiologically most abundant long-chain saturated FFA - elicits ER stress and which immediate signals commit β-cells to apoptosis...
July 24, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28731171/protective-role-of-pollen-typhae-total-flavone-against-the-palmitic-acid-induced-impairment-of-glucose-stimulated-insulin-secretion-involving-gpr40-signaling-in-ins-1-cells
#13
Xiao-Tao Feng, Hui-Ming Duan, Shuang-Lei Li
Prolonged elevated levels of free fatty acids (FFAs) contribute to the impairment of insulin secretion function of pancreatic β cells, a hallmark of type 2 diabetes, which is partly attributed to the dysfunction of G-protein-coupled receptor 40 (GPR40) signaling. Pollen Typhae total flavone (PTF), an extract from a Chinese herbal medicine named Pollen Typhae, has been reported to effectively treat type 2 diabetes, but the underlying mechanisms remain to be fully elucidated. In the present study, palmitic acid (PA), a saturated fatty acid, severely impaired glucose-stimulated insulin secretion (GSIS) in a time-dependent manner in INS-1 cells, and PTF treatment prevented the impairment in a dose-dependent manner...
July 18, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28727908/leveraging-a-clinical-phase-ib-proof-of-concept-study-for-the-gpr40-agonist-mk-8666-in-patients-with-type-2-diabetes-for-model-informed-phase-ii-dose-selection
#14
A W Krug, P Vaddady, R A Railkar, B J Musser, J Cote, Agh Ederveen, D G Krefetz, E DeNoia, A L Free, L Morrow, M V Chakravarthy, E Kauh, D A Tatosian, P A Kothare
GPR40 mediates free fatty acid-induced insulin secretion in beta cells. We investigated the safety, pharmacokinetics, and glucose response of MK-8666, a partial GPR40 agonist, after once-daily multiple dosing in type 2 diabetes patients. This double-blind, multisite, parallel-group study randomized 63 patients (placebo, n = 18; 50 mg, n = 9; 150 mg, n = 18; 500 mg, n = 18) for 14-day treatment. The results showed no serious adverse effects or treatment-related hypoglycemia. One patient (150-mg group) showed mild-to-moderate transaminitis at the end of dosing...
September 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28724742/the-myokine-irisin-is-released-in-response-to-saturated-fatty-acids-and-promotes-pancreatic-beta-cell-survival-and-insulin-secretion
#15
Annalisa Natalicchio, Nicola Marrano, Giuseppina Biondi, Rosaria Spagnuolo, Rossella Labarbuta, Immacolata Porreca, Angelo Cignarelli, Marco Bugliani, Piero Marchetti, Sebastio Perrini, Luigi Laviola, Francesco Giorgino
This study explored the role of irisin as a new pancreatic beta-cell secretagogue and survival factor and its potential role in the communication between skeletal muscle and pancreatic beta-cells under lipotoxic conditions. Recombinant irisin stimulated insulin biosynthesis and glucose-stimulated insulin secretion (GSIS) in a PKA-dependent manner, and prevented saturated fatty acid-induced apoptosis in human and rat pancreatic beta-cells, as well as in human and murine pancreatic islets, via AKT/BCL2 signaling...
July 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28680093/basal-hypersecretion-of-glucagon-and-insulin-from-palmitate-exposed-human-islets-depends-on-ffar1-but-not-decreased-somatostatin-secretion
#16
H Kristinsson, E Sargsyan, H Manell, D M Smith, S O Göpel, P Bergsten
In obesity fasting levels of both glucagon and insulin are elevated. In these subjects fasting levels of the free fatty acid palmitate are raised. We have demonstrated that palmitate enhances glucose-stimulated insulin secretion from isolated human islets via free fatty acid receptor 1 (FFAR1/GPR40). Since FFAR1 is also present on glucagon-secreting alpha-cells, we hypothesized that palmitate simultaneously stimulates secretion of glucagon and insulin at fasting glucose concentrations. In addition, we hypothesized that concomitant hypersecretion of glucagon and insulin was also contributed by reduced somatostatin secretion...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28654680/serum-fatty-acid-binding-protein-4-fabp4-concentration-is-associated-with-insulin-resistance-in-peripheral-tissues-a-clinical-study
#17
Risa Nakamura, Tsuyoshi Okura, Yohei Fujioka, Keisuke Sumi, Kazuhiko Matsuzawa, Shoichiro Izawa, Etsuko Ueta, Masahiko Kato, Shin-Ichi Taniguchi, Kazuhiro Yamamoto
Type 2 diabetes mellitus (T2DM) is caused by insulin resistance and β cell dysfunction. In recent studies reported that several markers associated with insulin sensitivity in skeletal muscle, Adiponectin and other parameters, such as fatty acid-binding protein (FABP4), have been reported to regulate insulin resistance, but it remains unclear which factor mostly affects insulin resistance in T2DM. In this cross-sectional study, we evaluated the relationships between several kinds of biomarkers and insulin resistance, and insulin secretion in T2DM and healthy controls...
2017: PloS One
https://www.readbyqxmd.com/read/28636047/decoding-the-regulatory-mechanism-of-glucose-and-insulin-induced-phosphatidylinositol-3-4-5-trisphosphate-dynamics-in-%C3%AE-cells
#18
Tagari Samanta, Peeyush Sharma, Dwijendra Kukri, Sandip Kar
In MIN6 pancreatic β-cells, glucose and insulin act in a synergistic manner to regulate the dynamics of Phosphatidylinositol (3,4,5)-trisphosphate (PIP3). However, the precise regulatory mechanism behind such an experimentally observed synergy is poorly understood. In this article, we propose a phenomenological mathematical model for studying the glucose and insulin driven PIP3 activation dynamics under various stimulatory conditions to unfold the mechanism responsible for the observed synergy. The modeling study reveals that the experimentally observed oscillation in PIP3 dynamics with disparate time scales for different external glucose doses is mainly orchestrated by the complex dynamic regulation of cytosolic Ca(2+) in β-cells...
July 25, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28612562/-pancreatic-%C3%AE-cell-dysfunction-and-apoptosis-induced-by-elevated-free-fatty-acids-synergize-with-hyperglycemia
#19
Hui-Wen Tan, Nai-Qian Zhao, Ye-Rong Yu, Li-Na Han, Xiang-Xun Zhang
OBJECTIVES: To analysis the effects of glucoxicity and lipotoxicity on the function and apoptosis of pancreatic β-cells. METHODS: The levels of circulating glucose and free fat acids (FFAs) were elevated by infusion dextrose and fat emulsion in high-fat obese rats. The insulin resistance model obese rats were divided into four gourp: obese group with saline infusion (OB-NS group, n=7), obese group with glucose infusion (OB-GS group, n=9), obese group with Lipid emulsion infusion (OB-FFA group, n=8), obese group with glucose and lipid emulsion infusion (OB-FG group, n=9)...
January 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28608561/angiogenic-and-restorative-abilities-of-human-mesenchymal-stem-cells-were-reduced-following-treatment-with-serum-from-diabetes-mellitus-type-2-patients
#20
Jafar Rezaie, Malek S Mehranjani, Reza Rahbarghazi, Mohammad A Shariatzadeh
This experiment investigated the impact of serum from patients with type 2 diabetes mellitus on the angiogenic behavior of human mesenchymal stem cells in vitro. Changes in the level of Ang-1, Ang-2, cell migration, and trans-differentiation into pericytes and endothelial lineage were monitored after 7 days. The interaction of mesenchymal stem cells with endothelial cells were evaluated using surface plasmon resonance technique. Paracrine restorative effect of diabetic stem cells was tested on pancreatic β cells...
June 13, 2017: Journal of Cellular Biochemistry
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