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Glucagon-like peptide

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https://www.readbyqxmd.com/read/29667232/the-pleiotropic-cardiovascular-effects-of-dipeptidyl-peptidase-4-inhibitors
#1
REVIEW
Angelo Avogaro, Gian Paolo Fadini
Patients with Type 2 Diabetes have an excess risk for cardiovascular disease. One of the several approaches, included in the Guidelines for the management of Type 2 Diabetes, is based on dipeptidyl peptidase 4 (DPP-4; also termed CD26) inhibitors (DPP-4-I), also called gliptins. Gliptins inhibit the degradation of glucagon-like peptide-1 GLP-1RA: this effect is associated with increased circulating insulin-to-glucagon ratio, and a consequent reduction of HbA1c. Beside incretin hormones, there are several proteins that may be affected by DPP-4 and its inhibition: among these some are relevant for the cardiovascular system homeostasis such as SDF-1α and its receptor CXCR4, brain natriuretic peptides, neuropeptide Y, and peptide YY...
April 17, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29667023/liraglutide-effects-on-upper-gastrointestinal-investigations-implications-prior-to-bariatric-surgery
#2
Renuca Modi, Peter Rye, Sarah Cawsey, Daniel W Birch, Arya M Sharma
Liraglutide is a glucagon-like peptide type 1 (GLP-1) analogue that is approved for long-term obesity management in North America. While bariatric surgery remains the gold standard for weight loss, an increasing number of patients are on liraglutide in the setting of ongoing workup for bariatric surgery. The presence of gastrointestinal symptoms prior to bariatric surgery may prompt testing for dysmotility, which affects surgical decision making. Here we report six cases where treatment with liraglutide was associated with reversible reduction in gastric and esophageal motility in screening for bariatric surgery...
April 17, 2018: Obesity Surgery
https://www.readbyqxmd.com/read/29665351/neuroendocrine-response-to-gaba-b-receptor-agonism-in-alcohol-dependent-individuals-results-from-a-combined-outpatient-and-human-laboratory-experiment
#3
Mehdi Farokhnia, Mikela B Sheskier, Mary R Lee, April N Le, Erick Singley, Sofia Bouhlal, Timmy Ton, Zhen Zhao, Lorenzo Leggio
Gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the nervous system, plays an important role in biobehavioral processes that regulate alcohol seeking, food intake, and stress response. The metabotropic GABA-B receptor has been investigated as a potential therapeutic target for alcohol use disorder, by using orthosteric agonists (e.g., baclofen) and positive allosteric modulators. Whether and how pharmacological manipulation of the GABA-B receptor, in combination with alcohol intake, may affect feeding- and stress-related neuroendocrine pathways remains unknown...
April 14, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29663628/exenatide-effects-on-gastric-emptying-and-oral-glucose-appearance-in-plasma-a-quantitative-assessment-using-an-integrative-systems-pharmacology-model
#4
Veronika Voronova, Kirill Zhudenkov, Robert C Penland, David W Boulton, Gabriel Helmlinger, Kirill Peskov
Glucagon-like peptide (GLP)-1 and synthetic GLP-1 receptor agonists (GLP-1RA) slow gastric emptying rate (GER), thereby decreasing the Glucose Rate of Appearance (GluRA) in plasma, which may contribute to postprandial plasma glucose (PPG) stabilization under GLP-1RA treatment. A quantitative systems pharmacology (QSP) approach was used to evaluate the effect of exenatide immediate release (IR), a short-acting GLP-1RA, on GER and GluRA. The proposed model is based on the data from multiple published sources including: (1) GLP-1 and exenatide plasma concentration-time profiles; (2) GER estimates under placebo, GLP-1 or exenatide IR dosing; (3) GluRA measurements upon food intake...
April 16, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29659969/aspartame-consumption-for-12-weeks-does-not-affect-glycemia-appetite-or-body-weight-of-healthy-lean-adults-in-a-randomized-controlled-trial
#5
Kelly A Higgins, Robert V Considine, Richard D Mattes
Background: Low-calorie sweeteners are often used to moderate energy intake and postprandial glycemia, but some evidence indicates that they may exacerbate these aims. Objective: The trial's primary aim was to assess the effect of daily aspartame ingestion for 12 wk on glycemia. Effects on appetite and body weight were secondary aims. Methods: One hundred lean [body mass index (kg/m2): 18-25] adults aged 18-60 y were randomly assigned to consume 0, 350, or 1050 mg aspartame/d (ASP groups) in a beverage for 12 wk in a parallel-arm design...
April 1, 2018: Journal of Nutrition
https://www.readbyqxmd.com/read/29659358/-role-of-the-enterocyte-in-type-2-diabetes-mellitus-associated-dyslipidemia
#6
Cecilia I Closs, Martín A Ruiz Diaz, Alberto M Cafferata, Damasia Becú-Villalobos, Juan P Nogueira
In type 2 diabetes mellitus there is an overproduction of chylomicron in the postprandial state that is associated with increased cardiovascular risk. Current evidence points out a leading role of enterocyte in dyslipidemia of type 2 diabetes mellitus, since it increases the production of apolipoprotein B-48 in response to a raise in plasma free fatty acids and glucose. The chylomicron metabolism is regulated by many factors apart from ingested fat, including hormonal and metabolic elements. More recently, studies about the role of gut hormones, have demonstrated that glucagon-like peptide-1 decreases the production of apolipoprotein B-48 and glucagon-like peptide-2 enhances it...
2018: Medicina
https://www.readbyqxmd.com/read/29659121/glucagon-like-peptide-1-ameliorates-cardiac-lipotoxicity-in-diabetic-cardiomyopathy-via-the-ppar%C3%AE-pathway
#7
Lujin Wu, Ke Wang, Wei Wang, Zheng Wen, Peihua Wang, Lei Liu, Dao Wen Wang
Lipotoxicity cardiomyopathy is the result of excessive accumulation and oxidation of toxic lipids in the heart. It is a major threat to patients with diabetes. Glucagon-like peptide-1 (GLP-1) has aroused considerable interest as a novel therapeutic target for diabetes mellitus because it stimulates insulin secretion. Here, we investigated the effects and mechanisms of the GLP-1 analog exendin-4 and the dipeptidyl peptidase-4 inhibitor saxagliptin on cardiac lipid metabolism in diabetic mice (DM). The increased myocardial lipid accumulation, oxidative stress, apoptosis, and cardiac remodeling and dysfunction induced in DM by low streptozotocin doses and high-fat diets were significantly reversed by exendin-4 and saxagliptin treatments for 8 weeks...
April 16, 2018: Aging Cell
https://www.readbyqxmd.com/read/29656185/exogenous-serp1-attenuates-restenosis-by-restoring-glp-1-receptor-activity-in-diabetic-rats-following-vascular-injury
#8
Lishuai Feng, Jianbo Wang, Xu Ma
The activity of glucagon-like peptide 1 (GLP-1R) is essential for preventing restenosis following vascular injury; however, the mechanism of dysfunctional GLP-1R glycosylation and ways to enhance the activity of GLP-1R on vascular surfaces in diabetic patients are poorly understood. In the present study, we investigated the N-glycosylation level and role of stress-associated endoplasmic reticulum protein 1 (SERP1) in preventing restenosis following carotid injury in diabetic rats. Our results showed that N-glycosylation levels in both rat aortic endothelial cells (RAOECs) and rat vascular smooth muscle cells (VSMCs) decreased gradually following glucose treatment in a concentration dependant manner...
April 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29656109/bile-acids-are-important-direct-and-indirect-regulators-of-the-secretion-of-appetite-and-metabolism-regulating-hormones-from-the-gut-and-pancreas
#9
Rune E Kuhre, Nicolai J Wewer Albrechtsen, Olav Larsen, Sara L Jepsen, Emilie Balk-Møller, Daniel B Andersen, Carolyn F Deacon, Kristina Schoonjans, Frank Reimann, Fiona M Gribble, Reidar Albrechtsen, Bolette Hartmann, Mette M Rosenkilde, Jens J Holst
OBJECTIVE: Bile acids (BAs) facilitate fat absorption and may play a role in glucose and metabolism regulation, stimulating the secretion of gut hormones. The relative importance and mechanisms involved in BA-stimulated secretion of appetite and metabolism regulating hormones from the gut and pancreas is not well described and was the purpose of this study. METHODS: The effects of bile acids on the secretion of gut and pancreatic hormones was studied in rats and compared to the most well described nutritional secretagogue: glucose...
March 17, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29655980/evaluation-of-novel-tgr5-agonist-in-combination-with-sitagliptin-for-possible-treatment-of-type-2-diabetes
#10
Sameer Agarwal, Santosh Sasane, Jeevan Kumar, Prashant Deshmukh, Hitesh Bhayani, Poonam Giri, Suresh Giri, Shubhangi Soman, Neelima Kulkarni, Mukul Jain
TGR5 is a member of G protein-coupled receptor (GPCR) superfamily, a promising molecular target for metabolic diseases. Activation of TGR5 promotes secretion of glucagon-like peptide-1 (GLP-1), which activates insulin secretion. A series of 2-thio-imidazole derivatives have been identified as novel, potent and orally efficacious TGR5 agonists. Compound 4d, a novel TGR5 agonist, in combination with Sitagliptin, a DPP-4 inhibitor, has demonstrated an adequate GLP-1 secretion and glucose lowering effect in animal models, suggesting a potential clinical option in treatment of type-2 diabetes...
April 5, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29651202/a-narrative-review-of-potential-future-antidiabetic-drugs-should-we-expect-more
#11
REVIEW
Gaurav Chikara, Pramod Kumar Sharma, Pradeep Dwivedi, Jaykaran Charan, Sneha Ambwani, Surjit Singh
Prevalence of diabetes mellitus, a chronic metabolic disease characterized by hyperglycemia, is growing worldwide. The majority of the cases belong to type 2 diabetes mellitus (T2DM). Globally, India ranks second in terms of diabetes prevalence among adults. Currently available classes of therapeutic agents are used alone or in combinations but seldom achieve treatment targets. Diverse pathophysiology and the need of therapeutic agents with more favourable pharmacokinetic-pharmacodynamics profile make newer drug discoveries in the field of T2DM essential...
April 2018: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/29650350/loss-of-dorsomedial-hypothalamic-glp-1-signaling-reduces-bat-thermogenesis-and-increases-adiposity
#12
Shin J Lee, Graciela Sanchez-Watts, Jean-Philippe Krieger, Angelica Pignalosa, Puck N Norell, Alyssa Cortella, Klaus G Pettersen, Dubravka Vrdoljak, Matthew R Hayes, Scott Kanoski, Wolfgang Langhans, Alan G Watts
OBJECTIVE: Glucagon-like peptide-1 (GLP-1) neurons in the hindbrain densely innervate the dorsomedial hypothalamus (DMH), a nucleus strongly implicated in body weight regulation and the sympathetic control of brown adipose tissue (BAT) thermogenesis. Therefore, DMH GLP-1 receptors (GLP-1R) are well placed to regulate energy balance by controlling sympathetic outflow and BAT function. METHODS: We investigate this possibility in adult male rats by using direct administration of GLP-1 (0...
March 21, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29644751/disease-modification-in-parkinson-s-disease-current-approaches-challenges-and-future-considerations
#13
REVIEW
Anthony E Lang, Alberto J Espay
The greatest unmet therapeutic need in Parkinson's disease is the development of treatment that slows the relentless progression of the neurodegenerative process. The concept of "disease modification" encompasses intervention types ranging from those designed to slow the underlying degeneration to treatments directed at regenerating or replacing lost neurons. To date all attempts to develop effective disease-modifying therapy have failed. Many reasons have been proposed for these failures including our rudimentary understanding of disease pathogenesis and the assumption that each targeted mechanisms of disease apply to most patients with the same clinical diagnosis...
April 11, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29628139/drug-repurposing-in-kidney-disease
#14
REVIEW
Usha Panchapakesan, Carol Pollock
Drug repurposing, is the re-tasking of known medications for new clinical indications. Advantages, compared to de novo drug development, include reduced cost and time to market plus the added benefit of a known pharmacokinetic and safety profiles. Suitable drug candidates are identified through serendipitous observations, data mining, or increased understanding of disease mechanisms. This review highlights drugs suited for repurposing in kidney disease. The main cause of mortality in patients with chronic kidney disease is cardiovascular disease...
April 6, 2018: Kidney International
https://www.readbyqxmd.com/read/29627317/intestinal-cart-is-a-regulator-of-gip-and-glp-1-secretion-and-expression
#15
L Shcherbina, A Lindqvist, A-H Thorén Fischer, E Ahlqvist, E Zhang, S E Falkmer, E Renström, J Koffert, H Honka, N Wierup
Impaired incretin effect is a culprit in Type 2 Diabetes. Cocaine- and amphetamine-regulated transcript (CART) is a regulatory peptide controlling pancreatic islet hormone secretion and beta-cell survival. Here we studied the potential expression of CART in enteroendocrine cells and examined the role of CART as a regulator of incretin secretion and expression. CART expression was found in glucose-dependent insulinotropic polypeptide (GIP)-producing K-cells and glucagon-like peptide-1 (GLP-1)-producing L-cells in human duodenum and jejunum and CART levels were increased 60 min after a meal in humans...
April 5, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29626654/geniposide-improves-repeated-restraint-stress-induced-depression-like-behavior-in-mice-by-ameliorating-neuronal-apoptosis-via-regulating-glp-1r-akt-signaling-pathway
#16
Yinghua Zhao, Hongyan Li, Fang Fang, Tingting Qin, Wei Xiao, Zhenzhong Wang, Shiping Ma
Geniposide (GP), a bioactive iridoid glycoside isolated from Gardenia jasminoides Ellis, as well as an agonist of Glucagon-like peptide-1 receptor (GLP-1R), has been reported to exhibit antidepressant-like effects in several rodent models. However, the underlying mechanisms remain obscure. In this study, we mainly investigated the antidepressant-like effects of GP and explored the possible mechanisms associated with GLP-1R signaling by using the repeated restraint stress (RRS)-induced depression model of mice...
April 4, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29626232/a-pre-meal-of-whey-proteins-induces-differential-effects-on-glucose-and-lipid-metabolism-in-subjects-with-the-metabolic-syndrome-a-randomised-cross-over-trial
#17
Ann Bjørnshave, Jens Juul Holst, Kjeld Hermansen
PURPOSE: Postprandial lipaemia (PPL), an independent risk factor for cardiovascular disease, is affected by composition and timing of meals. We evaluated if whey proteins (WP) consumed as a pre-meal before a fat-rich meal reduce postprandial triglyceride (TG) and apolipoprotein B-48 (ApoB-48) responses in subjects with the metabolic syndrome (MeS). METHODS: An acute, randomised, cross-over trial was conducted. 20 subjects with MeS consumed a pre-meal of 0, 10 or 20 g WP 15 min prior to a fat-rich meal...
April 6, 2018: European Journal of Nutrition
https://www.readbyqxmd.com/read/29623594/combination-treatment-of-sglt2-inhibitors-and-glp-1-receptor-agonists-symbiotic-effects-on-metabolism-and-cardiorenal-risk
#18
REVIEW
Edison Goncalves, David S H Bell
INTRODUCTION: When treating type 2 diabetes, drugs that cause hypoglycemia and weight gain should, if possible, be avoided. In addition, due to the increased incidence and prevalence of cardiovascular disease, cardiac events and heart failure, as well as the accelerated renal decompensation that may occur with type 2 diabetes, hypoglycemic agents that have the potential to lower cardiac and renal risk should be utilized as early as possible in the course of the disease. METHODS: This is a literature review of the efficacy of combined treatment with a glucagon-like peptide 1 (GLP-1) agonist and a sodium glucose cotransporter-2 (SGLT2) inhibitor in lowering glycated hemoglobin (HbA1c) level, cardiac risk, cardiac events and renal decompensation...
April 5, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29623579/pharmacokinetics-safety-and-tolerability-of-oral-semaglutide-in-subjects-with-renal-impairment
#19
Charlotte Granhall, Flemming L Søndergaard, Mette Thomsen, Thomas W Anderson
BACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, has been co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) as a tablet for oral administration. This trial (NCT02014259) investigated the pharmacokinetics, safety and tolerability of oral semaglutide in subjects with and without renal impairment. METHODS: Subjects were categorised as having normal renal function (n = 24), mild (n = 12), moderate (n = 12) or severe (n = 12) renal impairment, or end-stage renal disease (ESRD) requiring haemodialysis (n = 11) and received once-daily oral semaglutide (5 mg for 5 days followed by 10 mg for 5 days) in the fasting state, followed by 30 min fasting after dosing...
April 6, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29623219/management-strategies-for-posttransplant-diabetes-mellitus-after-heart-transplantation-a-review
#20
REVIEW
Matthew G Cehic, Nishant Nundall, Jerry R Greenfield, Peter S Macdonald
Posttransplant diabetes mellitus (PTDM) is a well-recognized complication of heart transplantation and is associated with increased morbidity and mortality. Previous studies have yielded wide ranging estimates in the incidence of PTDM due in part to variable definitions applied. In addition, there is a limited published data on the management of PTDM after heart transplantation and a paucity of studies examining the effects of newer classes of hypoglycaemic drug therapies. In this review, we discuss the role of established glucose-lowering therapies and the rationale and emerging clinical evidence that supports the role of incretin-based therapies (glucagon like peptide- (GLP-) 1 agonists and dipeptidyl peptidase- (DPP-) 4 inhibitors) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in the management of PTDM after heart transplantation...
2018: Journal of Transplantation
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