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fatty acids and insulin-secreting cells

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
July 20, 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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28606576/insulin-sensitizers-improve-the-glp-1-secretion-and-the-amount-of-intestinal-l-cells-on-high-fat-diet-induced-catch-up-growth
#14
Juan Zheng, Kang-Li Xiao, Lulu Chen, Chaodong Wu, Xiang Hu, Tianshu Zeng, Xiao-Qian Chen, Wen-Juan Li, Xiuling Deng, Huiqing Li, Yu-Ming Li
OBJECTIVE: The aim of this study was to investigate whether insulin resistance can result in impaired glucagon-like peptide (GLP)-1 secretion and to determine whether insulin-sensitizing drugs could improve the secretion of GLP-1 in catch-up growth rats. METHODS: Male Sprague Dawley rats were used to establish a catch-up growth model. At the end of weeks 6 and 14, these rats were euthanized to measure energy intake, body weight, plasma triacylglycerol, and nonesterified fatty acid...
July 2017: Nutrition
https://www.readbyqxmd.com/read/28576138/changes-in-pancreatic-histology-insulin-secretion-and-oxidative-status-in-diabetic-rats-following-treatment-with-ficus-deltoidea-and-vitexin
#15
Samsulrizal Nurdiana, Yong Meng Goh, Hafandi Ahmad, Sulaiman Md Dom, Nur Syimal'ain Azmi, Noor Syaffinaz Noor Mohamad Zin, Mahdi Ebrahimi
BACKGROUND: The potential application of Ficus deltoidea and vitexin for the management of symptomatologies associated with diabetes mellitus (DM) has gained much attention. However, less firm evidence comes from data to augment our understanding of the role of F. deltoidea and vitexin in protecting pancreatic β-cells. The aim of this study was to assess histological and oxidative stress changes in the pancreas of streptozotocin (STZ)-induced diabetic rats following F. deltoidea extract and vitexin treatment...
June 2, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28546450/fatty-acid-binding-protein-4-ap2-dependent-blt1r-expression-and-signaling
#16
Ann V Hertzel, Hongliang Xu, Michael Downey, Nicholas Kvalheim, David A Bernlohr
Previous studies have shown that reduced levels of the adipocyte fatty acid binding protein (FABP)4 (AFABP/aP2), result in metabolic improvement including potentiated insulin sensitivity and attenuated atherosclerosis. Mechanistically, pharmacologic or genetic inhibition of FABP4 in macrophages upregulates UCP2, attenuates reactive oxygen species (ROS) production, polarizes cells toward the anti-inflammatory M2 state, and reduces leukotriene (LT) secretion. At the protein level, FABP4 stabilizes LTA4 toward chemical hydrolysis, thereby potentiating inflammatory LTC4 synthesis...
July 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28523459/plasma-vascular-endothelial-growth-factor-b-levels-are-increased-in-patients-with-newly-diagnosed-type-2-diabetes-mellitus-and-associated-with-the-first-phase-of-glucose-stimulated-insulin-secretion-function-of-%C3%AE-cell
#17
J Wu, H Wei, H Qu, Z Feng, J Long, Q Ge, H Deng
PURPOSE: To detect plasma vascular endothelial growth factor B (VEGF-B) in individuals with different glucose tolerance and investigate the relationship between plasma VEGF-B levels and the first phase of glucose-stimulated insulin secretion. METHODS: A cross-sectional study was conducted involving 45 patients with newly diagnosed type 2 diabetes mellitus (T2DM), 37 patients with impaired glucose regulation (IGR), and 39 Normal glucose tolerance (NGT) subjects, all of whom underwent intravenous glucose tolerance test...
May 18, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28504618/butyrate-reduces-high-fat-diet-induced-metabolic-alterations-hepatic-steatosis-and-pancreatic-beta-cell-and-intestinal-barrier-dysfunctions-in-prediabetic-mice
#18
V A Matheus, Lcs Monteiro, R B Oliveira, D A Maschio, C B Collares-Buzato
In this study, we investigated the effect of diet supplementation with sodium butyrate (5% w/w), a short-chain fatty acid produced by the intestinal microbiota, on metabolic parameters, body adiposity, hepatic and pancreatic lipid accumulation, beta cell function/mass as well as on the structure and function of the tight junction-mediated intestinal epithelial barrier in both normal and obese/prediabetic C57 mice fed a regular (control) or high-fat diet for 60 days, respectively. Butyrate treatment significantly inhibited all the high-fat-induced metabolic dysfunctions evaluated, i...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28501410/effects-of-dietary-energy-allowance-and-decline-in-dry-matter-intake-during-the-dry-period-on-responses-to-glucose-and-insulin-in-transition-dairy-cows
#19
S Salin, A Vanhatalo, K Elo, J Taponen, R C Boston, T Kokkonen
We assessed whether high energy intake during the early dry period [144% of metabolizable energy (ME) requirements/d] followed by a gradual restriction of energy intake in the close-up dry period (119% of ME/d; HEI) impaired whole-body insulin sensitivity compared with a controlled energy intake (100% of ME/d; CEI) throughout the 6-wk dry period. Multiparous Ayrshire dairy cows (n = 16) were blocked by body weight, body condition score, and expected date of parturition and were used in a randomized complete block design until 10 d after parturition...
July 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28493909/hnf1%C3%AE-defect-influences-post-prandial-lipid-regulation
#20
Matthieu St-Jean, François Boudreau, André C Carpentier, Marie-France Hivert
PURPOSE: Hepatocyte nuclear factor 1 alpha (HNF1α) defects cause Mature Onset Diabetes of the Young type 3 (MODY3), characterized by defects in beta-cell insulin secretion. However, HNF1α is involved in many other metabolic pathways with relevance for monogenic or polygenic type 2 diabetes. We aimed to investigate gut hormones, lipids, and insulin regulation in response to a meal test in HNF1α defect carriers (MODY3) compared to non-diabetic subjects (controls) and type 2 diabetes (T2D)...
2017: PloS One
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