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fatty acids and insulin-secreting cells

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https://www.readbyqxmd.com/read/29337002/hypothalamic-inflammation-and-malfunctioning-glia-in-the-pathophysiology-of-obesity-and-diabetes-translational-significance
#1
REVIEW
Md Habibur Rahman, Anup Bhusal, Won-Ha Lee, In-Kyu Lee, Kyoungho Suk
Preclinical studies have suggested that chronic inflammation in the brain might be associated with multiple metabolic disorders, including obesity and diabetes. In particular, hypothalamic inflammation interferes with the endocrine system and modulates nutritional homeostasis, leading to metabolic alterations and consequent pathologies. With regard to the mechanisms underlying molecular and cellular pathogenesis, neurons, non-neuronal cells, and the crosstalk between them have gained particular attention. Specifically, malfunctioning glia have recently been implicated as an important component of pathological hypothalamic inflammation...
January 11, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29333376/anti-inflammatory-and-anti-obesity-properties-of-food-bioactive-components-effects-on-adipose-tissue
#2
REVIEW
Shasika Jayarathne, Iurii Koboziev, Oak-Hee Park, Wilna Oldewage-Theron, Chwan-Li Shen, Naima Moustaid-Moussa
Obesity is an epidemic and costly disease affecting 13% of the adult population worldwide. Obesity is associated with adipose tissue hypertrophy and hyperplasia, as well as pathologic endocrine alterations of adipose tissue including local and chronic systemic low-grade inflammation. Moreover, this inflammation is a risk factor for both metabolic syndrome (MetS) and insulin resistance. Basic and clinical studies demonstrate that foods containing bioactive compounds are capable of preventing both obesity and adipose tissue inflammation, improving obesity-associated MetS in human subjects and animal models of obesity...
December 2017: Preventive Nutrition and Food Science
https://www.readbyqxmd.com/read/29330456/20-hete-promotes-glucose-stimulated-insulin-secretion-in-an-autocrine-manner-through-ffar1
#3
Sorin Tunaru, Remy Bonnavion, Isabell Brandenburger, Jens Preussner, Dominique Thomas, Klaus Scholich, Stefan Offermanns
The long-chain fatty acid receptor FFAR1 is highly expressed in pancreatic β-cells. Synthetic FFAR1 agonists can be used as antidiabetic drugs to promote glucose-stimulated insulin secretion (GSIS). However, the physiological role of FFAR1 in β-cells remains poorly understood. Here we show that 20-HETE activates FFAR1 and promotes GSIS via FFAR1 with higher potency and efficacy than dietary fatty acids such as palmitic, linoleic, and α-linolenic acid. Murine and human β-cells produce 20-HETE, and the ω-hydroxylase-mediated formation and release of 20-HETE is strongly stimulated by glucose...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29317615/biotransformation-of-polyunsaturated-fatty-acids-to-bioactive-hepoxilins-and-trioxilins-by-microbial-enzymes
#4
Jung-Ung An, Yong-Seok Song, Kyoung-Rok Kim, Yoon-Joo Ko, Do-Young Yoon, Deok-Kun Oh
Hepoxilins (HXs) and trioxilins (TrXs) are involved in physiological processes such as inflammation, insulin secretion and pain perception in human. They are metabolites of polyunsaturated fatty acids (PUFAs), including arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid, formed by 12-lipoxygenase (LOX) and epoxide hydrolase (EH) expressed by mammalian cells. Here, we identify ten types of HXs and TrXs, produced by the prokaryote Myxococcus xanthus, of which six types are new, namely, HXB5, HXD3, HXE3, TrXB5, TrXD3 and TrXE3...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29311617/scfas-strongly-stimulate-pyy-production-in-human-enteroendocrine-cells
#5
P Larraufie, C Martin-Gallausiaux, N Lapaque, J Dore, F M Gribble, F Reimann, H M Blottiere
Peptide-YY (PYY) and Glucagon-Like Peptide-1 (GLP-1) play important roles in the regulation of food intake and insulin secretion, and are of translational interest in the field of obesity and diabetes. PYY production is highest in enteroendocrine cells located in the distal intestine, mirroring the sites where high concentrations of short chain fatty acids (SCFAs) are produced by gut microbiota. We show here that propionate and butyrate strongly increased expression of PYY but not GCG in human cell line and intestinal primary culture models...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29275428/association-of-nefa-composition-with-insulin-sensitivity-and-beta-cell-function-in-the-prospective-metabolism-and-islet-cell-evaluation-promise-cohort
#6
Luke W Johnston, Stewart B Harris, Ravi Retnakaran, Adria Giacca, Zhen Liu, Richard P Bazinet, Anthony J Hanley
AIMS/HYPOTHESIS: Our aim was to determine the longitudinal associations of individual NEFA with the pathogenesis of diabetes, specifically with differences in insulin sensitivity and beta cell function over 6 years in a cohort of individuals who are at risk for diabetes. METHODS: In the Prospective Metabolism and Islet Cell Evaluation (PROMISE) longitudinal cohort, 477 participants had serum NEFA measured at the baseline visit and completed an OGTT at three time points over 6 years...
December 24, 2017: Diabetologia
https://www.readbyqxmd.com/read/29273469/circulating-triacylglycerols-but-not-pancreatic-fat-associate-with-insulin-secretion-in-healthy-humans
#7
Bettina Nowotny, Sabine Kahl, Birgit Klüppelholz, Barbara Hoffmann, Guido Giani, Roshan Livingstone, Peter J Nowotny, Valerie Stamm, Christian Herder, Andrea Tura, Giovanni Pacini, Jong-Hee Hwang, Michael Roden
BACKGROUND: Loss of adequate insulin secretion for the prevailing insulin resistance is critical for the development of type 2 diabetes and has been suggested to result from circulating lipids (triacylglycerols [TG] or free fatty acids) and/or adipocytokines or from ectopic lipid storage in the pancreas. This study aimed to address whether circulating lipids, adipocytokines or pancreatic fat primarily associate with lower insulin secretion. SUBJECTS/METHODS: Nondiabetic persons (n=73), recruited from the general population, underwent clinical examinations, fasting blood drawing to measure TG and adipocytokines and oral glucose tolerance testing (OGTT) to assess basal and dynamic insulin secretion and sensitivity indices...
December 19, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29259758/sar-studies-of-indole-5-propanoic-acid-derivatives-to-develop-novel-gpr40-agonists
#8
Dong-Oh Yoon, Xiaodi Zhao, Dohyun Son, Jung Tae Han, Jaesook Yun, Dongyun Shin, Hyun-Ju Park
G-protein coupled receptor 40 (GPR40) has been considered to be an attractive drug target for the treatment of type 2 diabetes because of its role in free fatty acids-mediated enhancement of glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. A series of indole-5-propanoic acid compounds were synthesized, and their GPR40 agonistic activities were evaluated by nuclear factor of activated T-cells reporter assay and GSIS assay in the MIN-6 insulinoma cells. Three compounds, 8h (EC50 = 58.6 nM), 8i (EC50 = 37...
December 14, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29246479/elevated-plasma-levels-of-3-hydroxyisobutyric-acid-are-associated-with-incident-type-2-diabetes
#9
Adil Mardinoglu, Silvia Gogg, Luca A Lotta, Alena Stančáková, Annika Nerstedt, Jan Boren, Matthias Blüher, Ele Ferrannini, Claudia Langenberg, Nicholas J Wareham, Markku Laakso, Ulf Smith
Branched-chain amino acids (BCAAs) metabolite, 3-Hydroxyisobutyric acid (3-HIB) has been identified as a secreted mediator of endothelial cell fatty acid transport and insulin resistance (IR) using animal models. To identify if 3-HIB is a marker of human IR and future risk of developing Type 2 diabetes (T2D), we measured plasma levels of 3-HIB and associated metabolites in around 10,000 extensively phenotyped individuals. The levels of 3-HIB were increased in obesity but not robustly associated with degree of IR after adjusting for BMI...
December 7, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29225068/lysophosphatidylcholine-and-its-phosphorothioate-analogues-potentiate-insulin-secretion-via-gpr40-ffar1-gpr55-and-gpr119-receptors-in-a-different-manner
#10
Anna Drzazga, Hjalti Kristinsson, Maciej Sałaga, Hubert Zatorski, Maria Koziołkiewicz, Edyta Gendaszewska-Darmach, Peter Bergsten
Lysophosphatidylcholine (LPC) is an endogenous ligand for GPR119 receptor, mediating glucose-stimulated insulin secretion (GSIS). We demonstrate that LPC facilitates GSIS in MIN6 pancreatic β-cell line and murine islets of Langerhans by recognizing not only GPR119 but also GPR40 (free fatty acid receptor 1) and GPR55 activated by lysophosphatidylinositol. Natural LPCs are unstable when administered in vivo limiting their therapeutic value and therefore, we present phosphorothioate LPC analogues with increased stability...
December 8, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29217655/regulation-of-lipolytic-response-and-energy-balance-by-melanocortin-2-receptor-accessory-protein-mrap-in-adipocytes
#11
Xiaodong Zhang, Alicia M Saarinen, Latoya E Campbell, Elena A De Filippis, Jun Liu
MRAP is highly expressed in adrenal gland and adipose tissue. In adrenal cells, MRAP is essential for ACTH-induced activation of the cAMP/PKA pathway by melanocortin 2 receptor (MC2R), leading to glucocorticoid production and secretion. Although ACTH was known to stimulate PKA-dependent lipolysis, the functional involvement of MRAP in adipocyte metabolism remains incompletely defined. Herein, we found that knockdown or overexpression of MRAP in 3T3-L1 adipocytes reduced or increased ACTH-induced lipolysis, respectively...
December 7, 2017: Diabetes
https://www.readbyqxmd.com/read/29210640/fine-tuning-of-micrornas-in-type-2-diabetes-mellitus
#12
Juan A Rosado, Raquel Diez-Bello, Gines Maria Salido, I Jardin
Type 2 diabetes mellitus is a metabolic disease widely spread across industrialized countries. Sedentary lifestyle and unhealthy alimentary habits lead to obesity, boosting both glucose and fatty acid in the bloodstream and eventually, insulin resistance, pancreas inflammation and faulty insulin production or secretion, all of them very well-defined hallmarks of type 2 diabetes mellitus. miRNAs, are small sequences of non-coding RNA that may regulate several processes within the cells, fine-tuning protein expression, with an unexpected and subtle precision and in time-frames ranging from minutes to days...
December 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29210166/phytoceuticals-in-fenugreek-ameliorate-vldl-overproduction-and-insulin-resistance-via-the-insig-signaling-pathway
#13
Rituraj Khound, Jing Shen, Yongyan Song, Dipak Santra, Qiaozhu Su
SCOPE: This study aimed to characterize the effect of fenugreek (Trigonella foenum-graecum) seed and its phytoceutical trigonelline in anti-metabolic inflammation and ameliorating overproduction of very low density lipoprotein (VLDL) in insulin resistance. METHODS AND RESULTS: Two groups of genetic hyperlipidemic mice generated by depletion of cAMP responsive binding protein H (CREBH) were fed either a chow containing 2% fenugreek seed or vehicle for 7 weeks. Q-RT-PCR and immunoblotting analysis demonstrated that fenugreek seed containing diet inhibited hepatic SREBP-1c activation and the subsequent de novo lipogenesis by enhancing expression of insulin-inducible gene-1 (Insig-1) and gene-2 (Insig-2)...
December 6, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29196878/gut-microbiome-production-of-short-chain-fatty-acids-and-obesity-in-children
#14
REVIEW
Selvasankar Murugesan, Khemlal Nirmalkar, Carlos Hoyo-Vadillo, Matilde García-Espitia, Daniela Ramírez-Sánchez, Jaime García-Mena
Obesity has been a worldwide multifactorial epidemic malady for the last 2 decades. Changes in gut microbiota composition and its metabolites - short-chain fatty acids (SCFAs) - have been associated with obesity. Recent evidence suggests that SCFAs made by the gut microbiota may regulate directly or indirectly physiological and pathological processes in relation to obesity. We review the influence of gut microbiota in energy, glucose, and lipid homeostasis control via their metabolites. Gut microbial disturbances in obese children may have a role in their metabolism...
December 2, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/29176006/gpr120-mechanism-of-action-role-and-potential-for-medical-applications
#15
Hanna Karakuła-Juchnowicz, Joanna Róg, Dariusz Juchnowicz, Justyna Morylowska-Topolska
G protein-coupled receptors (GPCRs) constitute a family of transmembrane proteins that mediate many cellular processes. GPR120/FFAR4, a receptor from this family that is activated by fatty acids, has received considerable attention recently. This paper presents a literature review concerning the role of GPR120 and its mechanism of action in animal and human studies as well as the potential use of GPR120 for the treatment of chronic diseases. Two electronic databases - Medline and Google Scholar - were searched for available studies addressing the review topic that were written in English and published from 2000 to June 2017...
November 19, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/29126197/impaired-insulin-action-is-associated-with-increased-glucagon-concentrations-in-non-diabetic-humans
#16
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
#17
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
#18
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
#19
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
#20
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
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