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https://www.readbyqxmd.com/read/28730824/glucagon-like-peptide-1-analogues-exenatide-and-liraglutide-exert-inhibitory-effect-on-the-early-phase-of-liver-regeneration-after-partial-hepatectomy-in-rats
#1
J Fontana, O Kučera, V Mezera, M Anděl, Z Červinková
Glucagon-like peptide-1 (GLP-1) is an incretin known for proliferative and antiapoptotic effects on various tissues. Exenatide and Liraglutide are GLP-1 analogues used in clinical practice as antidiabetic drugs. Since GLP-1 and its analogues exert significant effect on liver metabolism and since changes in intermediary metabolism play an important role in the process of liver regeneration, we decided to determine the effect of Exenatide and Liraglutide on the early phase of liver regeneration and selected metabolic parameters in a model of 2/3 partial hepatectomy (PHx) in rats...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28725624/incretin-effect-of-urena-lobata-leaves-extract-on-structure-and-function-of-rats-islet-%C3%AE-cells
#2
Y Purnomo, D W Soeatmadji, S B Sumitro, M A Widodo
This study aims to determine the incretin effects of Urena lobata leaves extract on the structure and function of rats islet β-cells. This study utilizes male Sprague-Dawley rats divided into 2 control group and 3 test group (n = 5). Diabetic rats were induced with High Fructose Diet (HFD) and single dose intraperitoneal streptozotocin 25 mg/kg bw. Aqueous leaves extract of U. lobata was prepared by decoction methods and administrated orally with doses of 250, 500, and 1000 mg/kg bw for 4 weeks then incretin effect was evaluated by measuring serum GLP-1, insulin, and blood glucose levels...
July 2017: Journal of Traditional and Complementary Medicine
https://www.readbyqxmd.com/read/28724693/new-peptide-inhibitor-of-dipeptidyl-peptidase-iv-emdb-1-extends-the-half-life-of-glp-2-and-attenuates-colitis-in-mice-after-topical-administration
#3
Maciej Salaga, Anna Mokrowiecka, Marta Zielinska, Ewa Malecka-Panas, Radzislaw Kordek, Elzbieta Kamysz, Jakub Fichna
Protease inhibition has become a new possible approach in the inflammatory bowel disease (IBD) therapy. A serine exopeptidase, dipeptidyl peptidase IV (DPP IV) is responsible for inactivation of incretine hormone, glucagon-like peptide 2 (GLP-2), a potent stimulator of intestinal epithelium regeneration and growth. Recently we showed that the novel peptide analog of endomorphin-2, EMDB-1 is a potent blocker of DPP IV and has an inhibitory effect on gastrointestinal (GI) smooth muscle contractility. The aim of this study was to characterize the anti-inflammatory effect and mechanism of action of EMDB-1 in the mouse GI tract...
July 19, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28724607/renal-hemodynamic-effects-of-glucagon-like-peptide-1-agonist-are-mediated-by-nitric-oxide-but-not-prostaglandin
#4
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/28722834/effects-of-gip-glp-1-and-glp-1ras-on-bone-cell-metabolism
#5
Morten S S Hansen, Michaela Terencova, Jacob Frølich, Moustapha Kassem, Morten Frost
The relationship between gut and skeleton is increasingly recognised as part of the integrated physiology of the whole organism. The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the intestine in response to nutrient intake and exhibit several physiological functions including regulation of islet hormone secretion and glucose levels. A number of GLP-1 receptor agonists (GLP-1RAs) are currently used in treatment of type 2 diabetes and obesity. However, GIP and GLP-1 cognate receptors are widely expressed suggesting that incretin hormones mediate effects beyond control of glucose homeostasis, and reports on associations between incretin hormones and bone metabolism have emerged...
July 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28722242/therapeutic-application-of-gpr119-ligands-in-metabolic-disorders
#6
REVIEW
Jin Won Yang, Hyo Seon Kim, Yong-Won Choi, Young-Mi Kim, Keon Wook Kang
GPR119 belongs to the G protein-coupled receptor family, and exhibits dual modes of action upon ligand-dependent activation: pancreatic secretion of insulin in a glucose-dependent manner, and intestinal secretion of incretins. Hence, GPR119 has emerged as a promising target for treating type 2 diabetes mellitus without causing hypoglycemia. However, despite continuous efforts by many major pharmaceutical companies, no synthetic GPR119 ligand has been approved as a new class of anti-diabetic agents thus far, nor has one passed beyond phase II clinical studies...
July 18, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28719397/obesity-and-pancreatitis
#7
Biswajit Khatua, Bara El-Kurdi, Vijay P Singh
PURPOSE OF REVIEW: The obesity pandemic poses a unique set of problems for acute pancreatitis - both by increasing acute pancreatitis incidence, and worsening acute pancreatitis severity. This review explores these associations, underlying mechanisms, and potential therapies. RECENT FINDINGS: We review how the obesity associated increase in gallstones, surgical, and endoscopic interventions for obesity management, diabetes, and related medications such as incretin-based therapies and hypertriglyceridemia may increase the incidence of acute pancreatitis...
July 17, 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/28717862/practical-considerations-for-the-use-of-subcutaneous-treatment-in-the-management-of-dyslipidaemia
#8
REVIEW
Franck Boccara, Ricardo Dent, Luis Ruilope, Paul Valensi
Suboptimal drug adherence represents a major challenge to effective primary and secondary prevention of cardiovascular disease. While adherence is influenced by multiple considerations, polypharmacy and dosing frequency appear to be rate-limiting factors in patient satisfaction and subsequent adherence. The cardiovascular and metabolic therapeutic areas have recently benefited from a number of advances in drug therapy, in particular protease proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and incretin-based therapies, respectively...
July 17, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28698280/glycemic-control-after-metabolic-surgery-a-granger-causality-and-graph-analysis
#9
Elena Previti, Serenella Salinari, Alessandro Bertuzzi, Esmeralda Capristo, Stefan Bornstein, Geltrude Mingrone
To examine the contribution of Non-Esterified Fatty-Acids (NEFA) and incretin to insulin-resistance and diabetes amelioration after malabsorptive metabolic-surgery that dramatically reduces circulating NEFA. In fact, NEFA infusion reduces glucose-stimulated insulin secretion and high-fat diets predict diabetes development. Six healthy-controls, 11 obese and 10 Type-2-Diabetic (T2D) subjects were studied before and 1 month after Bilio-Pancreatic Diversion (BPD). Twenty-four hours plasma glucose, NEFA, insulin, C-peptide, glucagon-like peptide-1 (GLP1) and gastric-inhibitory-polypeptide (GIP) time courses were obtained and analyzed by Granger causality and graph analyses...
July 11, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28695626/mucosal-glucagon-like-peptide-1-glp-1-responses-are-mediated-by-calcitonin-gene-related-peptide-cgrp-in-the-mouse-colon-and-both-peptide-responses-are-area-specific
#10
I R Tough, R Moodaley, H M Cox
BACKGROUND: Glucagon-like peptide (GLP)-1 is an incretin hormone and its mimetics are proven antidiabetic and antiobesity drugs. GLP-1 exerts antimotility and mucosal proliferative activities but its epithelial ion transport effects are uncharacterized and these may contribute to the gastrointestinal (GI) disturbance, i.e., diarrhea experienced with some GLP-1 mimetics. Our aim was to establish GLP-1 agonist mechanisms and identify potential mucosal mediator(s) in the colonic tissue from C57BL/6J mice...
July 11, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28685028/bariatric-surgery-and-obesity-influence-on-the-incretins
#11
REVIEW
B Laferrère
The gut hormone incretins have an important physiological role in meal-related insulin release and post-prandial glucose control. In addition to weight loss, the incretin hormones have a role in glucose control after bariatric surgery. The release of incretins, and specifically of glucagon-like peptide (GLP)-1, in response to the ingestion of nutrients, is greatly enhanced after gastric bypass (RYGBP). The rapid transit of food from the gastric pouch to the distal ileum is responsible for the greater GLP-1 release after RYGBP...
December 2016: International Journal of Obesity Supplements
https://www.readbyqxmd.com/read/28685023/targeting-the-gut-to-treat-obesity-and-its-metabolic-comorbidities-focus-on-bariatric-surgery-view-from-the-chair
#12
A C Carpentier
Over the past decade, bariatric surgery emerged as the most effective treatment modality for obesity and its complications, especially type 2 diabetes. Initially introduced on the basis of their capacity to restrict food intake and/or induce dietary fat malabsorption, the current bariatric surgery procedures result in many more physiological changes that may also partly explain their potent and sustained anti-obesity and anti-diabetic effects. In the session 2 of the 17th International Symposium of the Université Laval Research Chair in Obesity, outstanding speakers have provided insight into novel clinical and pathophysiological aspects in bariatric surgery...
December 2016: International Journal of Obesity Supplements
https://www.readbyqxmd.com/read/28678048/antihyperglycemic-agents-and-cardiovascular-outcomes-recent-insights
#13
Harpreet S Bajaj, Bernard Zinman, Subodh Verma
PURPOSE OF REVIEW: To summarize cardiovascular outcome trials (CVOTs) with antihyperglycemic agents conducted since 2008 US Food and Drug Administration guidance. RECENT FINDINGS: A series of large CVOTs since 2008 have included patients with type 2 diabetes (T2D), who are otherwise treated according to standard of care. After the initial trials with incretin agents demonstrated cardiovascular safety, two recent CVOTs with currently available antihyperglycemic agents - EMPA-REG OUTCOME with empagliflozin and LEADER with liraglutide - show a significant reduction of the primary composite outcome, including a significant difference in the cardiovascular death end-point in both trials [EMPA-REG OUTCOME: hazard ratio = 0...
July 3, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/28667118/the-gluco-and-liporegulatory-and-the-vasodilatory-effects-of-glucose-dependent-insulinotropic-polypeptide-gip-are-abolished-by-an-antagonist-of-the-human-gip-receptor
#14
Meena Asmar, Ali Asmar, Lene Simonsen, Lærke Smidt Gasbjerg, Alexander Hovard Sparre-Ulrich, Mette Rosenkilde, Bolette Hartmann, Flemming Dela, Jens Juul Holst, Jens Bülow
A truncated form of human GIP, GIP(3-30)NH2, was recently identified as an antagonist of the human GIP receptor. This study examined the ability of GIP(3-30)NH2 to antagonize the physiological actions of GIP in glucose metabolism, subcutaneous abdominal adipose tissue blood flow (ATBF) and lipid metabolism in humans.Eight lean subjects were studied by measuring arterio-venous concentrations of metabolites and ATBF on three different occasions during hyperglycemic-hyperinsulinemic clamps with concomitant infusions of either GIP, GIP(3-30)NH2 or both GIP and GIP(3-30)NH2During GIP(3-30)NH2 alone and in combination with GIP, insulin levels and the total glucose amount infused to maintain the clamp were lower than during GIP alone...
June 30, 2017: Diabetes
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
#15
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/28662391/gold-nanoparticles-as-an-efficient-drug-delivery-system-for-glp-1-peptides
#16
Magdalena Pérez-Ortiz, Claudio Zapata-Urzúa, Gerardo A Acosta, Alejandro Álvarez-Lueje, Fernando Albericio, Marcelo J Kogan
In this work, the potential application of gold nanoparticles for GLP-1 analogues delivery was studied. For this purpose, the original sequence of the incretin GLP-1 was slightly modified in the C-terminal region by adding a cysteine residue to facilitate conjugation to the gold surface. The interaction between peptides and gold nanoparticles and also the colloid stability of the conjugates were studied by UV-vis spectrophotometry, TEM, IR and XPS spectroscopy. Moreover, the permeability of these conjugates was assayed using a Caco-2/goblet monolayer model...
June 19, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28660991/insulin-resistance-in-endocrine-disorders-treatment-options
#17
Anita Rogowicz-Frontczak, Anna Majchrzak, Dorota Zozulińska-Ziółkiewicz
Changes in sensitivity to insulin occur in the course of a number of endocrine disorders. Most of the hormones through their antagonistic action to insulin lead to increased hepatic glucose output and its decreased utilisation in peripheral tissues. Carbohydrate disorders observed in endocrine diseases result from the phenomenon of insulin resistance, and in some cases also a reduction in insulin secretion is present. Abnormalities of glucose metabolism are observed in acromegaly, but also in growth hormone deficiency, hypercortisolism in the course of Cushing's syndrome, hyper- or hypothyroidism, primary hyperparathyroidism, aldosteronism, pheochromocytoma, congenital hypertrophy of the adrenal glands, polycystic ovaries syndrome, hypogonadism, or other hormonally active neuroendocrine tumours...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28659588/the-dual-dpp4-inhibitor-and-gpr119-agonist-hbk001-regulates-glycemic-control-and-beta-cell-function-ex-and-in-vivo
#18
Yi Huan, Qian Jiang, Gang Li, Guoliang Bai, Tian Zhou, Shuainan Liu, Caina Li, Quan Liu, Sujuan Sun, Miaomiao Yang, Nan Guo, Xing Wang, Shusen Wang, Yaojuan Liu, Guanqiao Wang, Haihong Huang, Zhufang Shen
Glucagon like peptide-1 (GLP-1) plays a vital role in glucose homeostasis and sustaining β-cell function. Currently there are two major methods to enhance endogenous GLP-1 activity; inhibiting dipeptidyl peptidase-4 (DPP4) or activating G protein-coupled receptor 119 (GPR119). Here we describe and validate a novel dual-target compound, HBK001, which can both inhibit DPP4 and activate GPR119 ex and in vivo. We show that HBK001 can promote glucose-stimulated insulin secretion in mouse and human primary islets...
June 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28655715/incretin-secretion-in-humans-is-under-the-influence-of-cannabinoid-receptors
#19
Chee W Chia, Olga D Carlson, David D Liu, Isabel González-Mariscal, Sara Santa-Cruz Calvo, Josephine M Egan
The mechanisms regulating incretin secretion are not fully known. Human obesity is associated with altered incretin secretion and elevated endocannabinoid levels. Since cannabinoid receptors (CBRs) are expressed on incretin-secreting cells in rodents, we hypothesized that endocannabinoids are involved in the regulation of incretin secretion. We compared plasma glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) responses during oral glucose tolerance test (OGTT) in twenty lean and twenty obese participants from the Baltimore Longitudinal Study of Aging (BLSA)...
June 27, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28649604/combined-immunotherapy-with-anti-insulin-resistance-therapy-as-a-novel-therapeutic-strategy-against-neurodegenerative-diseases
#20
Yoshiki Takamatsu, Gilbert Ho, Wakako Koike, Shuei Sugama, Takato Takenouchi, Masaaki Waragai, Jianshe Wei, Kazunari Sekiyama, Makoto Hashimoto
Protein aggregation is a pathological hallmark of and may play a central role in the neurotoxicity in age-associated neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Accordingly, inhibiting aggregation of amyloidogenic proteins, including amyloid β and α-synuclein, has been a main therapeutic target for these disorders. Among various strategies, amyloid β immunotherapy has been extensively investigated in Alzheimer's disease, followed by similar studies of α-synuclein in Parkinson's disease...
2017: NPJ Parkinson's Disease
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