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https://www.readbyqxmd.com/read/28781108/exenatide-once-weekly-versus-placebo-in-parkinson-s-disease-a-randomised-double-blind-placebo-controlled-trial
#1
Dilan Athauda, Kate Maclagan, Simon S Skene, Martha Bajwa-Joseph, Dawn Letchford, Kashfia Chowdhury, Steve Hibbert, Natalia Budnik, Luca Zampedri, John Dickson, Yazhou Li, Iciar Aviles-Olmos, Thomas T Warner, Patricia Limousin, Andrew J Lees, Nigel H Greig, Susan Tebbs, Thomas Foltynie
BACKGROUND: Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has neuroprotective effects in preclinical models of Parkinson's disease. We investigated whether these effects would be apparent in a clinical trial. METHODS: In this single-centre, randomised, double-blind, placebo-controlled trial, patients with moderate Parkinson's disease were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg or placebo once weekly for 48 weeks in addition to their regular medication, followed by a 12-week washout period...
August 3, 2017: Lancet
https://www.readbyqxmd.com/read/28761132/exendin-4-reduces-food-intake-via-the-pi3k-akt-signaling-pathway-in-the-hypothalamus
#2
Yan Yang, Pique P Choi, Wanli W Smith, Weijie Xu, Delin Ma, Zachary A Cordner, Nu-Chu Liang, Timothy H Moran
Exendin-4 (EX-4), a glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce food intake and to increase proopiomelanocortin (POMC) gene expression in the hypothalamus. In this study, we examined the potential neural mechanisms by which these effects occur. Male Sprague Dawley rats were implanted with a cannula in the third ventricle of the brain through which an inhibitor of phosphatidylinositol-3 kinase (PI3K) (wortmannin) was administered, and EX-4 or vehicle was administered via intraperitoneal (IP) injection...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28757640/effects-of-peripheral-administration-of-a-neuromedin-u-receptor-2-selective-agonist-on-food-intake-and-body-weight-in-obese-mice
#3
T Kaisho, H Nagai, T Asakawa, N Suzuki, H Fujita, K Matsumiya, N Nishizawa, Y Kanematsu-Yamaki, K Dote, J-I Sakamoto, T Asami, S Takekawa
BACKGROUND: Neuromedin U (NMU) is a neuropeptide with various physiological functions including regulation of smooth-muscle contraction, blood pressure, stress responses, and feeding behaviors. NMU activates two distinct receptors, NMUR1 and NMUR2, which are predominantly expressed in peripheral tissues and the central nervous system, respectively. It is reported that the NMU signaling system regulates food intake and body weight via NMUR2, suggesting that an NMUR2 agonist exhibiting anorectic effects would be a potential therapy for obesity...
July 31, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28752054/serotonergic-modulation-of-the-activity-of-glp-1-producing-neurons-in-the-nucleus-of-the-solitary-tract-in-mouse
#4
Marie K Holt, Ida J Llewellyn-Smith, Frank Reimann, Fiona M Gribble, Stefan Trapp
OBJECTIVE: Glucagon-like peptide-1 (GLP-1) and 5-HT are potent regulators of food intake within the brain. GLP-1 is expressed by preproglucagon (PPG) neurons in the nucleus tractus solitarius (NTS). We have previously shown that PPG neurons innervate 5-HT neurons in the ventral brainstem. Here, we investigate whether PPG neurons receive serotonergic input and respond to 5-HT. METHODS: We employed immunohistochemistry to reveal serotonergic innervation of PPG neurons...
August 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28747063/dpp4-inhibitors-can-be-a-drug-of-choice-for-type-3-diabetes-a-mini-review
#5
Nehru Sai Suresh Chalichem, Chaitanya Gonugunta, Praveen Thaggikuppe Krishnamurthy, Basavan Duraiswamy
As well known to the scientific community, Alzheimer's disease (AD) is an irreversible neurodegenerative disease that ends up with impairment of memory and cognition due to neuronal and synapse loss. Patient's quality of life can be enhanced by targeting neurogenesis as a therapeutic paradigm. Moreover, several research evidences support the concept that AD is a type of metabolic disorder mediated by impairment in brain insulin responsiveness and energy metabolism. Growing evidence suggests that endogenous peptides such as glucagon-like peptide-1 (GLP-1) and stromal-derived factor-1α (SDF-1α) provide neuroprotection across a range of experimental models of AD...
January 1, 2017: American Journal of Alzheimer's Disease and Other Dementias
https://www.readbyqxmd.com/read/28724607/renal-hemodynamic-effects-of-glucagon-like-peptide-1-agonist-are-mediated-by-nitric-oxide-but-not-prostaglandin
#6
Scott Culver Thomson, Ali Kashkouli, Zhi Zhao Liu, Prabhleen Singh
The incretin hormone, glucagon like peptide-1 (GLP-1), is known for responding to dietary fat and carbohydrate. It elicits effects on pancreas, gut, and brain to stabilize blood glucose levels. We have previously reported that the GLP-1 agonist, exenatide, vasodilates the kidney and suppresses proximal reabsorption. The present study was undertaken to determine whether the renal effects of exenatide are mediated by nitric oxide (NO) and/or prostaglandins. Inulin clearance (GFR) and urine flow rate (UV) were measured in anesthetized rats before and during exenatide infusion (1 nmol/h iv)...
July 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28717164/glucagon-like-peptide-1-reduces-pancreatic-%C3%AE-cell-mass-through-hypothalamic-neural-pathways-in-high-fat-diet-induced-obese-rats
#7
Hisae Ando, Koro Gotoh, Kansuke Fujiwara, Manabu Anai, Seiichi Chiba, Takayuki Masaki, Tetsuya Kakuma, Hirotaka Shibata
We examined whether glucagon-like peptide-1 (GLP-1) affects β-cell mass and proliferation through neural pathways, from hepatic afferent nerves to pancreatic efferent nerves via the central nervous system, in high-fat diet (HFD)-induced obese rats. The effects of chronic administration of GLP-1 (7-36) and liraglutide, a GLP-1 receptor agonist, on pancreatic morphological alterations, c-fos expression and brain-derived neurotrophic factor (BDNF) content in the hypothalamus, and glucose metabolism were investigated in HFD-induced obese rats that underwent hepatic afferent vagotomy (VgX) and/or pancreatic efferent sympathectomy (SpX)...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710180/dipeptidyl-peptidase-4-regulates-hematopoietic-stem-cell-activation-in-response-to-chronic-stress
#8
Enbo Zhu, Lina Hu, Hongxian Wu, Limei Piao, Guangxian Zhao, Aiko Inoue, Weon Kim, Chenglin Yu, Wenhu Xu, Yasuko K Bando, Xiang Li, Yanna Lei, Chang-Ning Hao, Kyosuke Takeshita, Woo-Shik Kim, Kenji Okumura, Toyoaki Murohara, Masafumi Kuzuya, Xian Wu Cheng
BACKGROUND: DPP4 (Dipeptidyl peptidase-4)-GLP-1 (glucagon-like peptide-1) and its receptor (GLP-1R) axis has been involved in several intracellular signaling pathways. The Adrβ3 (β3-adrenergic receptor)/CXCL12 (C-X-C motif chemokine 12) signal was required for the hematopoiesis. We investigated the novel molecular requirements between DPP4-GLP-1/GLP-1 and Adrβ3/CXCL12 signals in bone marrow (BM) hematopoietic stem cell (HSC) activation in response to chronic stress. METHODS AND RESULTS: Male 8-week-old mice were subjected to 4-week intermittent restrain stress and orally treated with vehicle or the DPP4 inhibitor anagliptin (30 mg/kg per day)...
July 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28702330/neonatal-glp1r-activation-limits-adult-adiposity-by-durably-altering-hypothalamic-architecture
#9
Andrea V Rozo, Daniella A Babu, PoMan A Suen, David N Groff, Randy J Seeley, Rebecca A Simmons, Patrick Seale, Rexford S Ahima, Doris A Stoffers
OBJECTIVE: Adult obesity risk is influenced by alterations to fetal and neonatal environments. Modifying neonatal gut or neurohormone signaling pathways can have negative metabolic consequences in adulthood. Here we characterize the effect of neonatal activation of glucagon like peptide-1 (GLP-1) receptor (GLP1R) signaling on adult adiposity and metabolism. METHODS: Wild type C57BL/6 mice were injected with 1 nmol/kg Exendin-4 (Ex-4), a GLP1R agonist, for 6 consecutive days after birth...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28698254/mechanism-based-pharmacokinetic-pharmacodynamic-modeling-of-the-glucagon-like-peptide-1-receptor-agonist-exenatide-to-characterize-its-antiobesity-effects-in-diet-induced-obese-mice
#10
Shinji Iwasaki, Teruki Hamada, Ikumi Chisaki, Tomohiro Andou, Noriyasu Sano, Atsutoshi Furuta, Nobuyuki Amano
In addition to their potent antidiabetic effects, glucagon-like peptide-1 (GLP-1) analogs lower body weight in humans. Hence, agonistic targeting of the GLP-1 receptor could be a valid approach to target obesity. However, quantitative analyses of the pharmacokinetic/pharmacodynamic (PK/PD) relationship between GLP-1 analogs and their antiobesity effect have not been reported in either animals or humans. Therefore, the present study was performed to establish a mechanism-based PK/PD model of GLP-1 receptor agonists using the GLP-1 analog exenatide for the development of promising new antiobesity drugs...
September 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28685025/gut-hormones-such-as-amylin-and-glp-1-in-the-control-of-eating-and-energy-expenditure
#11
REVIEW
T A Lutz
The control of meal size is the best studied aspect of the control of energy balance, and manipulation of this system constitutes a promising target to treat obesity. A major part of this control system is based on gastrointestinal hormones such as glucagon-like peptide-1 (GLP-1) or amylin, which are released in response to a meal and which limit the size of an ongoing meal. Both amylin and GLP-1 have also been shown to increase energy expenditure in experimental rodents, but mechanistically we know much less how this effect may be mediated, which brain sites may be involved, and what the physiological relevance of these findings may be...
December 2016: International Journal of Obesity Supplements
https://www.readbyqxmd.com/read/28683293/a-specific-gut-microbiota-dysbiosis-of-type-2-diabetic-mice-induces-glp-1-resistance-through-an-enteric-no-dependent-and-gut-brain-axis-mechanism
#12
Estelle Grasset, Anthony Puel, Julie Charpentier, Xavier Collet, Jeffrey E Christensen, François Tercé, Rémy Burcelin
No abstract text is available yet for this article.
July 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28669754/the-impact-of-gut-hormones-on-the-neural-circuit-of-appetite-and-satiety-a-systematic-review
#13
REVIEW
Davide Zanchi, Antoinette Depoorter, Laura Egloff, Sven Haller, Laura Mählmann, Undine E Lang, Jürgen Drewe, Christoph Beglinger, André Schmidt, Stefan Borgwardt
The brain-gut-axis is an interdependent system affecting neural functions and controlling our eating behaviour. In recent decades, neuroimaging techniques have facilitated its investigation. We systematically looked into functional and neurochemical brain imaging studies investigating how key molecules such as ghrelin, glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), cholecystokinin (CCK), leptin, glucose and insulin influence the function of brain regions regulating appetite and satiety. Of the 349 studies published before July 2016 identified in the database search, 40 were included (27 on healthy and 13 on obese subjects)...
June 29, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28666800/a-novel-glp-1-gip-dual-agonist-is-more-effective-than-liraglutide-in-reducing-inflammation-and-enhancing-gdnf-release-in-the-mptp-mouse-model-of-parkinson-s-disease
#14
Ziyue Yuan, Dongfang Li, Peng Feng, Guofang Xue, Chenhui Ji, Guanglai Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is one of the risk factors for Parkinson's disease (PD). Insulin desensitisation has been observed in the brains of patients, which may promote neurodegeneration. Incretins are a family of growth factors that can re-sensitise insulin signalling. We have previously shown that mimetics of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP) mouse model of PD...
June 27, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28665013/epigenetic-regulation-by-g9a-glp-complex-ameliorates-amyloid-beta-1-42-induced-deficits-in-long-term-plasticity-and-synaptic-tagging-capture-in-hippocampal-pyramidal-neurons
#15
Mahima Sharma, Tobias Dierkes, Sreedharan Sajikumar
Altered epigenetic mechanisms are implicated in the cognitive decline associated with neurodegenerative diseases such as in Alzheimer's disease (AD). AD is the most prevalent form of dementia worldwide; amyloid plaques and neurofibrillary tangles are the histopathological hallmarks of AD. We have recently reported that the inhibition of G9a/GLP complex promotes long-term potentiation (LTP) and its associative mechanisms such as synaptic tagging and capture (STC). However, the role of this complex in plasticity impairments remains elusive...
June 30, 2017: Aging Cell
https://www.readbyqxmd.com/read/28657399/combination-sglt2-inhibitor-and-glp-1-receptor-agonist-therapy-a-complementary-approach-to-the-treatment-of-type-2-diabetes
#16
Robert S Busch, Michael P Kane
Among persons with type 2 diabetes (t2d), the development of glucose intolerance involves dysfunction in several organs and tissues, including the muscle, liver, pancreas, kidney, gastrointestinal tract, adipose tissue, and brain. individuals with t2d typically have a number of comorbidities, including hypertension, hyperlipidemia, and being overweight or obese, and are, consequently, at high cardiovascular risk. guidelines recommend a comprehensive care strategy that includes treatment of diabetes-related complications and comorbidities beyond those related to hyperglycemia...
June 28, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28624122/glucagon-like-peptide-1-and-insulin-synergistically-activate-vagal-afferent-neurons
#17
Yusaku Iwasaki, Chayon Goswami, Toshihiko Yada
Intestinal glucagon-like peptide-1 (GLP-1) and pancreatic insulin, released postprandially, commonly regulate glucose metabolism. Recent clinical experience indicates that the GLP-1R agonist and insulin in combination, compared to insulin alone, results in better glycemic and weight controls in type 2 diabetic patients. These observations suggest possible interactive effect of these hormones. These hormones, in addition to peripherally controlling glycemia, exert central regulation of food intake and glucose metabolism, the effect at least partly mediated by signaling to the brain via the vagal afferents...
May 25, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28611211/metabolic-and-neuroprotective-effects-of-dapagliflozin-and-liraglutide-in-diabetic-mice
#18
Paul Millar, Nupur Pathak, Vadivel Parthsarathy, Anthony J Bjourson, Maurice O'Kane, Varun Pathak, R Charlotte Moffett, Peter R Flatt, Victor A Gault
This study assessed the metabolic and neuroprotective actions of the sodium glucose cotransporter-2 inhibitor dapagliflozin in combination with the GLP-1 agonist liraglutide in dietary-induced diabetic mice. Mice administered low-dose streptozotocin (STZ) on a high-fat diet received dapagliflozin, liraglutide, dapagliflozin-plus-liraglutide (DAPA-Lira) or vehicle once-daily over 28 days. Energy intake, body weight, glucose and insulin concentrations were measured at regular intervals. Glucose tolerance, insulin sensitivity, hormone and biochemical analysis, dual-energy X-ray absorptiometry densitometry, novel object recognition, islet and brain histology were examined...
September 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28573460/brain-glp-1-igf-1-signaling-and-autophagy-mediate-exendin-4-protection-against-apoptosis-in-type-2-diabetic-rats
#19
Emanuel Candeias, Inês Sebastião, Susana Cardoso, Cristina Carvalho, Maria Sancha Santos, Catarina Resende Oliveira, Paula I Moreira, Ana I Duarte
Type 2 diabetes (T2D) is a modern socioeconomic burden, mostly due to its long-term complications affecting nearly all tissues. One of them is the brain, whose dysfunctional intracellular quality control mechanisms (namely autophagy) may upregulate apoptosis, leading to cognitive dysfunction and Alzheimer disease (AD). Since impaired brain insulin signaling may constitute the crosslink between T2D and AD, its restoration may be potentially therapeutic herein. Accordingly, the insulinotropic anti-T2D drugs from glucagon-like peptide-1 (GLP-1) mimetics, namely, exendin-4 (Ex-4), could be a promising therapy...
June 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28558993/estradiol-modulates-the-anorexic-response-to-central-glucagon-like-peptide-1
#20
Calyn B Maske, Christine M Jackson, Sarah J Terrill, Lisa A Eckel, Diana L Williams
Estrogens suppress feeding in part by enhancing the response to satiation signals. Glucagon-like peptide 1 (GLP-1) acts on receptor populations both peripherally and centrally to affect food intake. We hypothesized that modulation of the central GLP-1 system is one of the mechanisms underlying the effects of estrogens on feeding. We assessed the anorexic effect of 0, 1, and 10μg doses of GLP-1 administered into the lateral ventricle of bilaterally ovariectomized (OVX) female rats on a cyclic regimen of either 2μg β-estradiol-3-benzoate (EB) or oil vehicle 30min prior to dark onset on the day following hormone treatment...
July 2017: Hormones and Behavior
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