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https://www.readbyqxmd.com/read/28334990/insulin-resistance-and-exendin-4-treatment-for-multiple-system-atrophy
#1
Fares Bassil, Marie-Hélène Canron, Anne Vital, Erwan Bezard, Yazhou Li, Nigel H Greig, Seema Gulyani, Dimitrios Kapogiannis, Pierre-Olivier Fernagut, Wassilios G Meissner
Multiple system atrophy is a fatal sporadic adult-onset neurodegenerative disorder with no symptomatic or disease-modifying treatment available. The cytopathological hallmark of multiple system atrophy is the accumulation of α-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Impaired insulin/insulin-like growth factor-1 signalling (IGF-1) and insulin resistance (i.e. decreased insulin/IGF-1) have been reported in other neurodegenerative disorders such as Alzheimer's disease. Increasing evidence also suggests impaired insulin/IGF-1 signalling in multiple system atrophy, as corroborated by increased insulin and IGF-1 plasma concentrations in multiple system atrophy patients and reduced IGF-1 brain levels in a transgenic mouse model of multiple system atrophy...
March 14, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28331351/long-term-management-of-type-2-diabetes-with-glucagon-like-peptide-1-receptor-agonists
#2
REVIEW
Hamish Courtney, Rahul Nayar, Chinnadorai Rajeswaran, Ravi Jandhyala
Continuously reducing excess blood glucose is a primary goal for the management of type 2 diabetes (T2D). Most patients with T2D require glucose-lowering medications to achieve and maintain adequate glycemic control; however, treatment failure may occur, limiting treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an emerging therapeutic class that can be prescribed for patients instead of basal insulin after the failure of oral therapies. Recent studies have focused on the durability and tolerability of long-term GLP-1RA therapy...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28330952/effects-of-insulin-and-the-glucagon-like-peptide-1-receptor-agonist-liraglutide-on-the-kidney-proteome-in-db-db-mice
#3
Leena Liljedahl, Jenny Norlin, James N McGuire, Peter James
Diabetes mellitus (DM) is a worldwide disease that affects 9% of the adult world population and type 2 DM accounts for 90% of those. A common consequence of DM is kidney complications, which could lead to kidney failure. We studied the potential effects of treatment with insulin and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide on the diabetic kidney proteome through the use of the db/db mouse model system and mass spectrometry (MS). Multivariate analyses revealed distinct effects of insulin and liraglutide on the db/db kidney proteome, which was seen on the protein levels of, for example, pterin-4 α-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor-1α (PCBD1), neural precursor cell expressed developmentally down-regulated-8 (NEDD8), transcription elongation factor-B polypeptide-1 (ELOC) and hepcidin (HEPC)...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28329747/influence-of-dipeptidyl-peptidase-iv-inhibitor-sitagliptin-on-extracellular-signal-regulated-kinases-1-2-signaling-in-rats-with-diabetic-nephropathy
#4
Xiaojun Ren, Gaohong Liu, Yanhong Wang, Wan Zhang, Fuping Xue, Rongshan Li, Weimin Yu
The protective effects of sitagliptin on the kidneys of rats with diabetic nephropathy (DN) and its influence on extracellular signal-regulated kinases 1/2 (ERK1/2) signaling were investigated. Male Wistar rats (n = 40) were randomly assigned to normal control, DN, low-dose sitagliptin intervention (ST1), or high-dose sitagliptin intervention (ST2) groups. Animals were euthanized after a 16-week treatment, and blood glucose (BG), glycosylated hemoglobin (HbA1c), urinary albumin excretion rate (AER), serum creatinine (Scr), creatinine clearance rate (Ccr), active glucagon-like peptide-1 (GLP-1) levels, kidney hypertrophy index, and renal pathohistology were determined...
March 23, 2017: Pharmacology
https://www.readbyqxmd.com/read/28327597/molecular-signaling-underlying-bulleyaconitine-a-baa-induced-microglial-expression-of-prodynorphin
#5
Teng-Fei Li, Hai-Yun Wu, Yi-Rui Wang, Xin-Yan Li, Yong-Xiang Wang
Bulleyaconitine (BAA) has been shown to possess antinociceptive activities by stimulation of dynorphin A release from spinal microglia. This study investigated its underlying signal transduction mechanisms. The data showed that (1) BAA treatment induced phosphorylation of CREB (rather than NF-κB) and prodynorphin expression in cultured primary microglia, and antiallodynia in neuropathy, which were totally inhibited by the CREB inhibitor KG-501; (2) BAA upregulated phosphorylation of p38 (but not ERK or JNK), and the p38 inhibitor SB203580 (but not ERK or JNK inhibitor) and p38β gene silencer siRNA/p38β (but not siRNA/p38α) completely blocked BAA-induced p38 phosphorylation and/or prodynorphin expression, and antiallodynia; (3) BAA stimulated cAMP production and PKA phosphorylation, and the adenylate cyclase inhibitor DDA and PKA inhibitor H-89 entirely antagonized BAA-induced prodynorphin expression and antiallodynia; (4) The Gs-protein inhibitor NF449 completely inhibited BAA-increased cAMP level, prodynorphin expression and antiallodynia, whereas the antagonists of noradrenergic, corticotrophin-releasing factor, A1 adenosine, formyl peptide, D1/D2 dopamine, and glucagon like-peptide-1 receptors failed to block BAA-induced antiallodynia...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28326005/bioactivity-of-food-peptides-biological-response-of-rats-to-bovine-milk-whey-peptides-following-acute-exercise
#6
Carolina Soares Moura, Pablo Christiano Barboza Lollo, Priscila Neder Morato, Eder Muller Risso, Jaime Amaya-Farfan
Background: Several physiologically beneficial effects of consuming a whey protein hydrolysate (WPH) have been attributed to the greater availability of bioactive peptides. Aims: The aim was to investigate the effect of four branched-chain amino acid- (BCAA-)containing dipeptides, present in WPH, on immune modulation, stimulation of HSP expression, muscle protein synthesis, glycogen content, satiety signals and the impact of these peptides on the plasma free amino acid profiles. Methods: The animals were divided in groups: control (rest, without gavage), vehicle (water), L-isoleucyl-L-leucine (lle-Leu), L-leucyl-L-isoleucine (Leu-lle), L-valyl-Lleucine (Val-Leu), L-leucyl-L-valine (Leu-Val) and WPH...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28325801/insulin-and-glucagon-like-peptide-1-receptor-agonist-combination-therapy-in-type-2-diabetes-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#7
REVIEW
Maria Ida Maiorino, Paolo Chiodini, Giuseppe Bellastella, Annalisa Capuano, Katherine Esposito, Dario Giugliano
OBJECTIVE: The combination of basal insulin plus a glucagon-like peptide 1 receptor agonist (GLP-1RA) has been proposed as a treatment option to intensify insulin therapy in type 2 diabetes. We performed a meta-analysis of randomized controlled trials (RCTs) comparing this combination strategy to other injectable antidiabetes treatments on metabolic control in adult patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted an electronic search until November 2016 on many electronic databases to identify RCTs assessing changes in HbA1c, proportion of patients at HbA1c target ≤7% (53 mmol/mol), hypoglycemia, and weight change...
April 2017: Diabetes Care
https://www.readbyqxmd.com/read/28325589/all-cause-mortality-in-patients-with-diabetes-under-glucagon-like-peptide-1-agonists-a-population-based-open-cohort-study
#8
K A Toulis, W Hanif, P Saravanan, B H Willis, T Marshall, B Kumarendran, K Gokhale, S Ghosh, K K Cheng, P Narendran, G N Thomas, K Nirantharakumar
AIM: The glucagon-like peptide-1 receptor agonist (GLP1a) liraglutide has been described to benefit patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk. However, there are still uncertainties relating to these cardiovascular benefits: whether they also apply to an unselected diabetic population that includes low-risk patients, represent a class-effect, and could be observed in a real-world setting. METHODS: We conducted a population-based, retrospective open cohort study using data derived from The Health Improvement Network database between Jan 2008 to Sept 2015...
March 18, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28325479/the-role-of-pancreatic-preproglucagon-in-glucose-homeostasis-in-mice
#9
Adam P Chambers, Joyce E Sorrell, April Haller, Karen Roelofs, Chelsea R Hutch, Ki-Suk Kim, Ruth Gutierrez-Aguilar, Bailing Li, Daniel J Drucker, David A D'Alessio, Randy J Seeley, Darleen A Sandoval
Glucagon-like peptide 1 (GLP-1) is necessary for normal gluco-regulation, and it has been widely presumed that this function reflects the actions of GLP-1 released from enteroendocrine L cells. To test the relative importance of intestinal versus pancreatic sources of GLP-1 for physiological regulation of glucose, we administered a GLP-1R antagonist, exendin-[9-39] (Ex9), to mice with tissue-specific reactivation of the preproglucagon gene (Gcg). Ex9 impaired glucose tolerance in wild-type mice but had no impact on Gcg-null or GLP-1R KO mice, suggesting that Ex9 is a true and specific GLP-1R antagonist...
March 9, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28323117/absorption-metabolism-and-excretion-of-the-glp-1-analogue-semaglutide-in-humans-and-nonclinical-species
#10
Lene Jensen, Hans Helleberg, Ad Roffel, Jan Jaap van Lier, Inga Bjørnsdottir, Palle Jacob Pedersen, Everton Rowe, Julie Derving Karsbøl, Mette Lund Pedersen
Semaglutide is a human glucagon-like peptide-1 analogue in clinical development for the treatment of type 2 diabetes. The absorption, metabolism and excretion of a single 0.5mg/450μCi [16.7MBq] subcutaneous dose of [(3)H]-radiolabelled semaglutide was investigated in healthy human subjects and compared with data from nonclinical studies. Radioactivity in blood, plasma, urine and faeces was determined in humans, rats and monkeys; radioactivity in expired air was determined in humans and rats. Metabolites in plasma, urine and faeces were quantified following profiling and radiodetection...
March 16, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28321905/differential-increments-of-basal-glucagon-like-1-peptide-concentration-among-slc47a1-rs2289669-genotypes-were-associated-with-inter-individual%C3%A2-variability-in%C3%A2-glycaemic-response-to-metformin-in-chinese-people-with-newly-diagnosed-type-2-diabetes
#11
H Liang, W Xu, L Zhou, W Yang, J Weng
AIM: To elucidate the effects of rs2289669, an intron variant of the SLC47A1 gene, on metformin responses in Chinese people with newly diagnosed Type 2 diabetes. METHODS: We conducted a nationwide, multicentre, prospective clinical trial, in which rs2289669 was genotyped, using Sequenom, in 291 participants. The changes in HbA1c were compared among rs2289669 genotypes, and associations with rs2289669 were evaluated using linear regression analysis. RESULTS: We found that, compared with participants with a homozygous G allele, those carrying the minor A allele had significantly greater HbA1c reduction and increases in basal glucagon-like peptide-1 concentration...
March 21, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28321312/preserved-glucagon-like-peptide-1-responses-to-oral-glucose-but-reduced-incretin-effect-insulin-secretion-and-sensitivity-in-young-asians-with-type-2-diabetes-mellitus
#12
Toh Peng Yeow, Giovanni Pacini, Andrea Tura, Chee Peng Hor, Shueh Lin Lim, Florence Hui Sieng Tan, Chin Voon Tong, Janet Yeow Hua Hong, Fuziah Md Zain, Jens Juul Holst, Wan Nazaimoon Wan Mohamud
OBJECTIVE: Youth onset type 2 diabetes mellitus (YT2DM) is a globally rising phenomenon with substantial Asians representation. The understanding of its pathophysiology is derived largely from studies in the obese African-American and Caucasian populations, while studies on incretin effect are scarce. We examined the insulin resistance, β-cell function (BC), glucagon-like peptide (GLP)-1 hormone and incretin effect in Asian YT2DM. RESEARCH DESIGN AND METHODS: This case-control study recruited 25 Asian YT2DM and 15 healthy controls, matched for gender, ethnicity and body mass index...
2017: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/28319060/the-anti-diabetic-drug-exenatide-a-glucagon-like-peptide-1-receptor-agonist-counteracts-hepatocarcinogenesis-through-camp-pka-egfr-stat3-axis
#13
M Zhou, M T S Mok, H Sun, A W Chan, Y Huang, A S L Cheng, G Xu
Epidemiological studies have demonstrated a close association of type 2 diabetes and hepatocellular carcinoma (HCC). Exenatide (Ex-4), a potent diabetes drug targeting glucagon-like peptide-1 receptor (GLP-1R), is protective against non-alcoholic fatty liver disease (NAFLD). However, the Ex-4 function and GLP-1R status have yet been explored in HCC. Herein we investigated the effect of Ex-4 in diethylnitrosamine (DEN)-treated mice consuming control or high-fat high-carbohydrate diet. Administration of Ex-4 significantly improved obesity-induced hyperglycemia and hyperlipidemia and reduced HCC multiplicity in obese DEN-treated mice, in which suppressed proliferation and induced apoptosis were confined to tumor cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28318339/exendin-4-does-not-modify-growth-or-apoptosis-of-human-colon-cancer-cells
#14
He Wenjing, Yu Shuang, Li Weisong, Xiao Haipeng
AIM: Glucagon-like peptide-1 (GLP-1) receptor agonists are a kind of very popular antidiabetes drugs. They promote cell proliferation and survival through activation of signaling pathways in human islet cells involving phosphate idylinositol 3 kinase (PI3K) and extracellular regulated kinases 1 and 2 (ERK1/2), which are frequently activated in human colon cancer cells. Then, it is possible that taking GLP-1 receptor (GLP-1R) agonists persistently would induce proliferation of β cells as well as colon cancer cells...
March 20, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28317734/aroma-compound-diacetyl-suppresses-glucagon-like-peptide-1-production-and-secretion-in-stc-1-cells
#15
Triona McCarthy, Christine Bruen, Fiona O'Halloran, Harriet Schellekens, Kieran Kilcawley, John F Cryan, Linda Giblin
Diacetyl is a volatile flavour compound that has a characteristic buttery aroma and is widely used in the flavour industry. The aroma of a food plays an important role in food palatability and thus intake. This study investigates the effect of diacetyl on the satiety hormone, glucagon-like peptide (GLP-1), using the enteroendocrine cell line, STC-1. Diacetyl decreased proglucagon mRNA and total GLP-1 from glucose stimulated STC-1 cells. This dampening effect on GLP-1 appears to be mediated by increasing intracellular cAMP levels, increasing synthesis of the G protein coupled receptor, GPR120, and its recruitment to the cell surface...
August 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28315693/central-glp-1-receptor-activation-modulates-cocaine-evoked-phasic-dopamine-signaling-in-the-nucleus-accumbens-core
#16
Samantha M Fortin, Mitchell F Roitman
Drugs of abuse increase the frequency and magnitude of brief (1-3s), high concentration (phasic) dopamine release events in terminal regions. These are thought to be a critical part of drug reinforcement and ultimately the development of addiction. Recently, metabolic regulatory peptides, including the satiety signal glucagon-like peptide-1 (GLP-1), have been shown to modulate cocaine reward-driven behavior and sustained dopamine levels after cocaine administration. Here, we use fast-scan cyclic voltammetry (FSCV) to explore GLP-1 receptor (GLP-1R) modulation of dynamic dopamine release in the nucleus accumbens (NAc) during cocaine administration...
March 15, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28315374/glp-1-analogue-cjc-1131-prevents-amyloid-%C3%AE-protein-induced-impirments-of-spatial-memory-and-synaptic-plasticity-in-rats
#17
Sheng-Xiao Zhang, Hong-Yan Cai, Xiao-Wen Ma, Li Yuan, Jun Zhang, Zhao-Jun Wang, Yu-Feng Li, Jin-Shun Qi
Although amyloid β protein (Aβ) has been recognized as one of the main pathological characteristics in the brain of Alzheimer's disease (AD), the effective strategies against Aβ neurotoxicity are still deficient up to now. Glucagon-like peptide 1 (GLP-1), a natural gut hormone, was found to be effective in modulating insulin signaling and neural protection, but short half-life limited its clinical application in AD treatment. CJC-1131, a newly designed GLP-1 analogue with very longer half-life, has shown good effectiveness in the treatment of type 2 diabetes mellitus (T2DM)...
March 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28315192/discrete-choice-experiment-attribute-selection-using-a-multinational-interview-study-treatment-features-important-to-patients-with-type-2-diabetes-mellitus
#18
Anna Rydén, Stephanie Chen, Emuella Flood, Beverly Romero, Susan Grandy
INTRODUCTION: Methods for discrete choice experiment (DCE) attribute and attribute-level selection have not yet been firmly established and are rarely reported in detail. This paper describes a qualitative study designed to inform the development of a DCE survey designed to examine preferences for glucagon-like peptide-1 receptor agonist (GLP-1RA) treatments among patients with type 2 diabetes mellitus. METHODS: The study involved a literature review, interviews with clinical experts, and interviews with GLP-1RA-experienced (i...
March 17, 2017: Patient
https://www.readbyqxmd.com/read/28304141/evidence-connecting-old-new-and-neglected-glucose-lowering-drugs-to-bile-acid-induced-glp-1-secretion-a-review
#19
REVIEW
Martin L Kårhus, Andreas Brønden, David P Sonne, Tina Vilsbøll, Fillip K Knop
Bile acids are amphipathic water-soluble steroid-based molecules best known for their important lipid-solubilizing role in the assimilation of fat. Recently, bile acids have emerged as metabolic integrators with glucose-lowering potential. Among a variety of gluco-metabolic effects, bile acids have been demonstrated to modulate the secretion of the gut-derived incretin hormone glucagon-like peptide-1 (GLP-1), possibly via the transmembrane receptor Takeda G protein-coupled receptor 5 (TGR5) and the nuclear farnesoid X receptor (FXR), in intestinal L cell...
March 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28303626/lixisenatide-as-add-on-treatment-among-patients-with-different-%C3%AE-cell-function-levels-as-assessed-by-homa-%C3%AE-index
#20
Riccardo C Bonadonna, Lawrence Blonde, Mikhail Antsiferov, Rachele Berria, Pierre Gourdy, Mensud Hatunic, Viswanathan Mohan, Michael Horowitz
BACKGROUND: The effect of lixisenatide - a prandial once-daily glucagon-like peptide-1 receptor agonist - on glycaemic control in patients with inadequately controlled type 2 diabetes (T2DM), stratified by baseline β-cell function was assessed. METHODS: The 24-week GetGoal-M, -P and -S trials evaluated the efficacy and safety of lixisenatide in combination with oral antidiabetic agents. This post hoc analysis used data from patients receiving lixisenatide in these trials, divided into matched cohorts by propensity scoring and stratified according to baseline homeostasis model assessment of β-cell function (HOMA-β) index levels (high HOMA-β: > median HOMA-β [28...
March 17, 2017: Diabetes/metabolism Research and Reviews
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