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fatty acids and insulin-secreting cells

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https://www.readbyqxmd.com/read/29126197/impaired-insulin-action-is-associated-with-increased-glucagon-concentrations-in-non-diabetic-humans
#1
Anu Sharma, Ron T Varghese, Meera Shah, Chiara Dalla Man, Claudio Cobelli, Robert A Rizza, Kent R Bailey, Adrian Vella
Context: Abnormal glucagon concentrations contribute to hyperglycemia but the mechanism(s) of α-cell dysfunction in prediabetes are unclear. Objective: We sought to determine the relative contributions of insulin secretion and action to α-cell dysfunction in non-diabetic subjects across the spectrum of glucose tolerance. Design: This was a cross-sectional study. A subset of subjects (n = 120) was studied in the presence and absence of free fatty acid (FFA) elevation, achieved by infusion of intralipid + heparin, to cause insulin resistance...
November 6, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29068547/structural-basis-for-the-agonist-action-at-free-fatty-acid-receptor-1-ffa1r-or-gpr40
#2
REVIEW
Daniel A Rodrigues, Pedro de Sena M Pinheiro, Thayssa T S C Ferreira, Sreekanth Thota, Carlos A M Fraga
G-protein-coupled receptor 40 (GPR40) was recently identified as an interesting target for treatment of type II diabetes. The high level of expression in pancreatic beta cells and the dependence of glucose on stimulating the secretion of insulin led to great excitement in this field. The identification of this target was followed by the development of a series of agonists with great potential for the treatment of diabetes. All known agonists have the presence of a pharmacophoric carboxylic acid group in their structure, which makes several polar interactions at the binding site of this receptor...
October 25, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29031729/point-mutation-of-ffar1-abrogates-fatty-acid-dependent-insulin-secretion-but-protects-against-hfd-induced-glucose-intolerance
#3
Sibylle Sabrautzki, Gabriele Kaiser, Gerhard K H Przemeck, Felicia Gerst, Estela Lorza-Gil, Madhura Panse, Tina Sartorius, Miriam Hoene, Susan Marschall, Hans-Ulrich Häring, Martin Hrabě de Angelis, Susanne Ullrich
OBJECTIVE: The fatty acid receptor 1 (FFAR1/GPR40) mediates fatty acid-dependent augmentation of glucose-induced insulin secretion (GIIS) in pancreatic β-cells. Genetically engineered Ffar1-knockout/congenic mice univocally displayed impaired fatty acid-mediated insulin secretion, but in vivo experiments delivered controversial results regarding the function of FFAR1 in glucose homeostasis and liver steatosis. This study presents a new coisogenic mouse model carrying a point mutation in Ffar1 with functional consequence...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031723/inhibition-of-cholinergic-potentiation-of-insulin-secretion-from-pancreatic-islets-by-chronic-elevation-of-glucose-and-fatty-acids-protection-by-casein-kinase-2-inhibitor
#4
Nicolai M Doliba, Qin Liu, Changhong Li, Pan Chen, Chengyang Liu, Ali Naji, Franz M Matschinsky
OBJECTIVES: Chronic hyperlipidemia and hyperglycemia are characteristic features of type 2 diabetes (T2DM) that are thought to cause or contribute to β-cell dysfunction by "glucolipotoxicity." Previously we have shown that acute treatment of pancreatic islets with fatty acids (FA) decreases acetylcholine-potentiated insulin secretion. This acetylcholine response is mediated by M3 muscarinic receptors, which play a key role in regulating β-cell function. Here we examine whether chronic FA exposure also inhibits acetylcholine-potentiated insulin secretion using mouse and human islets...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29016744/novel-effects-of-dapagliflozin-on-epicardial-adipose-tissue-with-insulin-resistance-high-levels-of-inflammatory-chemokines-production-and-low-differentiation-ability
#5
Esther Díaz-Rodríguez, Rosa M Agra, Ángel L Fernández, B Adrio, Tomás García-Caballero, José R González-Juanatey, Sonia Eiras
Aims: In patients with cardiovascular disease, epicardial adipose tissue (EAT) is characterized by insulin resistance, high pro-inflammatory chemokines and low differentiation ability. Since dapagliflozin reduces body fat and cardiovascular events in diabetic patients, we wanted to know its effect on EAT and subcutaneous adipose tissue (SAT). Methods and results: Adipose samples were obtained from 52 patients undergoing heart surgery. Sodium-glucose cotransporter 2 (SGLT2) expression was determined by real time PCR (n = 20), Western blot and immunohistochemistry...
September 11, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28987595/acylated-apelin-13-amide-analogues-exhibit-enzyme-resistance-and-prolonged-insulin-releasing-glucose-lowering-and-anorexic-properties
#6
Finbarr P M O'Harte, Vadivel Parthsarathy, Christopher Hogg, Peter R Flatt
The adipokine, apelin has many biological functions but its activity is curtailed by rapid plasma degradation. Fatty acid derived apelin analogues represent a new and exciting avenue for the treatment of obesity-diabetes. This study explores four novel fatty acid modified apelin-13 analogues, namely, (Lys(8)GluPAL)apelin-13 amide, pGlu(Lys(8)GluPAL)apelin-13 amide, Lys(8)GluPAL(Tyr(13))apelin-13 and Lys(8)GluPAL(Val(13))apelin-13. Fatty acid modification extended the half-life of native apelin-13 to >24 h in vitro...
October 4, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28980863/addition-of-exogenous-sodium-palmitate-increases-the-iapp-insulin-mrna-ratio-via-gpr40-in-human-endoc-%C3%AE-h1-cells
#7
Camilla Krizhanovskii, Rikard G Fred, Marie E Oskarsson, Gunilla T Westermark, Nils Welsh
BACKGROUND: Enhanced IAPP production may contribute to islet amyloid formation in type 2 diabetes. The objective of this study was to determine the effects of the saturated fatty acid palmitate on IAPP levels in human β-cells. METHODS: EndoC-βH1 cells and human islets were cultured in the presence of sodium palmitate. Effects on IAPP/insulin mRNA expression and secretion were determined using real-time qPCR/ELISA. Pharmacological activators and/or inhibitors and RNAi were used to determine the underlying mechanisms...
August 2017: Upsala Journal of Medical Sciences
https://www.readbyqxmd.com/read/28980402/is-palmitoleic-acid-a-plausible-non-pharmacological-strategy-to-prevent-or-control-chronic-metabolic-and-inflammatory-disorders
#8
REVIEW
Camila O Souza, Gretchen K Vannice, José C Rosa Neto, Philip C Calder
Although dietary fatty acids can modulate metabolic and immune responses, the effects of palmitoleic acid (16:1n-7) remain unclear. Since this monounsaturated fatty acid was described as a lipokine, studies with cell culture and rodent models have suggested it enhances whole body insulin sensitivity, stimulates insulin secretion by β-cells, increases hepatic fatty acid oxidation, improves the blood lipid profile, and alters macrophage differentiation. However, human studies report elevated blood levels of palmitoleic acid in people with obesity and metabolic syndrome...
October 5, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28965028/angiopoietin-like-protein-8-an-attractive-biomarker-for-the-evaluation-of-subjects-with-insulin-resistance-and-related-disorders
#9
REVIEW
Su Wang, Xiafei Hong, Zhigang Tu, Guoyue Yuan
Insulin resistance is prevalent worldwide and is associated with many metabolic diseases, in particular, type 2 diabetes mellitus (T2DM), obesity, nonalcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS) and metabolic syndrome (MetS). Angiopoietin-like protein 8 (ANGPTL8), a newly-identified secreted protein composing of 198 amino acids, is enriched in the liver of human. Considering its promising potential for β-cell proliferation and therapeutic prospect for diabetes, ANGPTL8 has aroused extensive interests...
November 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28941594/fenofibrate-attenuates-fatty-acid-induced-islet-%C3%AE-cell-dysfunction-and-apoptosis-via-inhibiting-the-nf-%C3%AE%C2%BAb-mif-dependent-inflammatory-pathway
#10
Shuang Zheng, Xingxing Ren, Tingting Han, Yawen Chen, Huiying Qiu, Wei Liu, Yaomin Hu
BACKGROUND: Fatty acid-induced lipotoxicity and macrophage migration inhibitory factor (MIF) affect pancreatic β-cell function, and may promote the development of diabetes mellitus. However, the association of lipotoxicity with MIF and the effect of Fenofibrate on β-cell function remain unknown. METHODS: LPL+/- mice and MIN6 cells stimulated with palmitic acid (PA) were utilized as models of lipid metabolism disorders. Factors associated with insulin secretion and apoptosis were assessed in the presence or absence of Fenofibrate...
September 20, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28933059/function-and-dysfunction-of-adipose-tissue
#11
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
#12
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
#13
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
#14
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
#15
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...
November 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
#16
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
#17
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
#18
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
#19
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...
September 30, 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
#20
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...
December 2017: Cell Death and Differentiation
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