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https://www.readbyqxmd.com/read/29782892/a-glp-1-cck-fusion-peptide-harnesses-the-synergistic-effects-on-metabolism-of-cck-1-and-glp-1-receptor-agonism-in-mice
#1
David C Hornigold, Emma Roth, Victor Howard, Sarah Will, Stephanie Oldham, Matthew P Coghlan, Clemence Blouet, James L Trevaskis
Combination approaches for the treatment of metabolic diseases such as obesity and diabetes are becoming increasingly relevant. Co-administration of a glucagon-like peptide-1 receptor (GLP-1R) agonist with a cholecystokinin receptor-1 (CCKR1) agonist exert synergistic effects on weight loss in obese rodents. Here, we report on the effects of a novel fusion peptide (C2816) comprised of a stabilized GLP-1R agonist, AC3174, and a CCKR1-selective agonist, AC170222. C2816 was constructed such that AC3174 was linked to the N-terminus of AC170222, thus preserving the C-terminal amide of the CCK moiety...
May 18, 2018: Appetite
https://www.readbyqxmd.com/read/29779196/retrospective-analysis-of-an-insulin-to-liraglutide-switch-in-patients-with-type-2-diabetes-mellitus
#2
Eveline Bruinstroop, Laura Meyer, Catherine B Brouwer, Diana E van Rooijen, P Sytze van Dam
INTRODUCTION: Insulin and the GLP-1 receptor agonist liraglutide are both effective in reaching glycemic targets. The efficacy of an insulin-to-liraglutide switch in an obese population with concurrent use of sulfonylurea and metformin is unknown. We assessed the efficacy and determinants of success of an insulin-to-liraglutide switch in these patients. METHODS: In a retrospective study we analyzed all patients that underwent an insulin-to-liraglutide switch during routine medical care (January 2009-February 2015)...
May 19, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29778663/glp-1-receptor-agonists-and-reduction-of-cardiometabolic-risk-potential-underlying-mechanisms
#3
REVIEW
Manfredi Rizzo, Dragana Nikolic, Angelo Maria Patti, Carlo Mannina, Giuseppe Montalto, Brooke S McAdams, Ali A Rizvi, Francesco Cosentino
Type 2 diabetes mellitus (T2DM) is a metabolic condition with an elevated impact on cardiovascular (CV) risk. The innovative therapeutic approaches for T2DM - incretin-based therapies (IBTs), including glucagon-like peptide 1 (GLP-1) receptor agonists, have become popular and more widely used in recent years. The available scientific data from clinical studies and clinical practice highlights their beyond glucose-lowering effects, which is achieved without any increase in hypoglycaemia. The former effects include reduction in body weight, lipids, blood pressure, inflammatory markers, oxidative stress, endothelial dysfunction, and subclinical atherosclerosis, thus reducing and potentially preventing CV events...
May 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777704/dietary-mung-bean-protein-reduces-high-fat-diet-induced-weight-gain-by-modulating-host-bile-acid-metabolism-in-a-gut-microbiota-dependent-manner
#4
Akiho Nakatani, Xuan Li, Junki Miyamoto, Miki Igarashi, Hitoshi Watanabe, Asuka Sutou, Keita Watanabe, Takayasu Motoyama, Nobuhiko Tachibana, Mitsutaka Kohno, Hiroshi Inoue, Ikuo Kimura
The 8-globulin-rich mung bean protein (MPI) suppresses hepatic lipogenesis in rodent models and reduces fasting plasma glucose and insulin levels in obese adults. However, its effects on mitigating high fat diet (HFD)-induced obesity and the mechanism underlying these effects remain to be elucidated. Herein, we examined the metabolic phenotype, intestinal bile acid (BA) pool, and gut microbiota of conventionally raised (CONV-R) male C57BL/6 mice and germ-free (GF) mice that were randomized to receive either regular HFD or HFD containing mung bean protein isolate (MPI) instead of the dairy protein present in regular HFD...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777703/bacterial-metabolite-s-equol-modulates-glucagon-like-peptide-1-secretion-from-enteroendocrine-l-cell-line-glutag-cells-via-actin-polymerization
#5
Kazuki Harada, Shoko Sada, Hidekazu Sakaguchi, Mai Takizawa, Rika Ishida, Takashi Tsuboi
S-equol is one of gut bacterial metabolites produced from soybean isoflavone daizein. While S-equol is known to promote glucose-induced insulin secretion from pancreatic β cells, whether S-equol affects glucagon-like peptide-1 (GLP-1) secretion from enteroendoceine L cells remains unclear. Here we assessed the effect of S-equol on GLP-1 secretion from mouse enteroendocrine L cell line GLUTag cells. GLUTag cells expressed GPR30 and estrogen receptors, which are putative S-equol receptors. Application of S-equol induced an increase in intracellular Ca2+ levels via GPR30...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777582/comparative-study-of-liraglutide-and-insulin-glargine-on-glycemic-control-and-pancreatic-%C3%AE-cell-function-in-db-db-mice
#6
Yanli Li, Jia Zheng, Yunfeng Shen, Wangen Li, Meimei Liu, Jun Wang, Surong Zhu, Meihua Wu
BACKGROUND The aim of this study was to compare the effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, and insulin glargine, a long-acting insulin analog, on glycemic control and pancreatic β-cell function in db/db mice. MATERIAL AND METHODS Eight-week-old male db/db mice (n=40) were divided into five groups: the vehicle-treated group (VG) (n=8); the insulin glargine-treated group (GG) (dose, 450 mg/kg) (n=8), the low-dose liraglutide-treated group (LLG) (dose, 75 μg/kg) (n=8), the mid-dose liraglutide-treated group (MLG) (150 μg/kg) (n=8), and the high-dose liraglutide-treated group (HLG) (300 μg/kg) (n=8), treated with subcutaneous injection once daily, from 8-14 weeks-of-age...
May 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29776968/liraglutide-modulates-appetite-and-body-weight-via-glp-1r-expressing-glutamatergic-neurons
#7
Jessica M Adams, Hongjuan Pei, Darleen A Sandoval, Randy J Seeley, Rui B Chang, Stephen D Liberles, David P Olson
Glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved weight loss drugs. Despite their widespread use, the sites of action through which GLP-1R agonists (GLP1RAs) impact appetite and body weight are still not fully understood. Here, we determined whether GLP-1Rs in either GABAergic or glutamatergic neurons are necessary for the acute and chronic effects of the GLP1RA liraglutide on food intake, visceral illness, body weight and neural network activation. We found that mice lacking GLP-1Rs in vGAT -expressing GABAergic neurons responded identically to controls in all parameters measured, whereas deletion of GLP-1Rs in vGlut2 -expressing glutamatergic neurons eliminated liraglutide-induced weight loss and visceral illness and severely attenuated its effects on feeding...
May 18, 2018: Diabetes
https://www.readbyqxmd.com/read/29776414/glp-i-secretion-in-healthy-and-diabetic-wistar-rats-in-response-to-aqueous-extract-of-momordica-charantia
#8
Gulzar Ahmad Bhat, Haseeb A Khan, Abdullah S Alhomida, Poonam Sharma, Rambir Singh, Bilal Ahmad Paray
BACKGROUND: Diabetes mellitus is one of the major global health disorders increasing at an alarming rate in both developed and developing countries. The objective of this study was to assess the effect of aqueous extract of Momordica charantia (AEMC) on fasting blood glucose (FBG), tissue glycogen, glycosylated haemoglobin, plasma concentrations of insulin and GLP-1 hormone (glucagon-like peptide 1) in healthy and diabetic wistar rats. METHODS: Male Wistar rats (both normal and diabetic) were treated with AEMC by gavaging (300 mg/kg body wt/day for 28 days)...
May 18, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29776406/the-effect-of-dpp-4-inhibition-to-improve-functional-outcome-after-stroke-is-mediated-by-the-sdf-1%C3%AE-cxcr4-pathway
#9
Fausto Chiazza, Harald Tammen, Hiranya Pintana, Grazyna Lietzau, Massimo Collino, Thomas Nyström, Thomas Klein, Vladimer Darsalia, Cesare Patrone
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are approved drugs for the treatment of hyperglycemia in patients with type 2 diabetes. These effects are mainly mediated by inhibiting endogenous glucagon-like peptide-1 (GLP-1) cleavage. Interestingly, gliptins can also improve stroke outcome in rodents independently from GLP1. However, the underlying mechanisms are unknown. Stromal cell-derived factor-1α (SDF-1α) is a DPP-4 substrate and CXCR4 agonist promoting beneficial effects in injured brains...
May 19, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29775245/subunits-of-the-dna-polymerase-alpha-primase-complex-promote-notch-mediated-proliferation-with-discrete-and-shared-functions-in-c-elegans-germline
#10
Dong Suk Yoon, Dong Seok Cha, Mohammad A Alfhili, Brett D Keiper, Myon-Hee Lee
Notch receptor signaling is a highly conserved cell communication system in most multicellular organisms and plays a critical role at several junctures in animal development. In C. elegans, GLP-1/Notch signaling is essential for both germline stem cell maintenance and germ cell proliferation during gonad development. Here, we show that subunits (POLA-1, DIV-1, PRI-1, and PRI-2) of the DNA polymerase alpha-primase complex are required for germ cell proliferation in response to GLP-1/Notch signaling in different tissues at different developmental stages...
May 18, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29773934/iglarlixi-a-new-once-daily-fixed-ratio-combination-of-basal-insulin-glargine-and-lixisenatide-for-the-management-of-type-2-diabetes
#11
Debbie Hinnen, Jodi Strong
Background: Patients with type 2 diabetes require treatment intensification to maintain glycemic control. Clinician reluctance, patient injection fears, hypoglycemia, weight gain, or other objections may lead to clinical inertia, whereby therapy is not intensified and patients live with uncontrolled hyperglycemia and increased risk for complications. Initiation of injectable therapy with a glucagon-like peptide (GLP)-1 receptor agonist and/or basal insulin is a recommended option for patients with type 2 diabetes inadequately controlled on one or more oral agents...
May 2018: Diabetes Spectrum: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/29772784/capsaicin-in-metabolic-syndrome
#12
REVIEW
Sunil K Panchal, Edward Bliss, Lindsay Brown
Capsaicin, the major active constituent of chilli, is an agonist on transient receptor potential vanilloid channel 1 (TRPV1). TRPV1 is present on many metabolically active tissues, making it a potentially relevant target for metabolic interventions. Insulin resistance and obesity, being the major components of metabolic syndrome, increase the risk for the development of cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. In vitro and pre-clinical studies have established the effectiveness of low-dose dietary capsaicin in attenuating metabolic disorders...
May 17, 2018: Nutrients
https://www.readbyqxmd.com/read/29771387/functional-brown-adipose-tissue-and-sympathetic-activity-after-cold-exposure-in-humans-with-type-1-narcolepsy
#13
Lotte Hahn Enevoldsen, Marie Tindborg, Nichlas Lindegaard Hovmand, Christina Christoffersen, Helga Ellingsgaard, Charlotte Suetta, Bente Merete Stallknecht, Poul Joergen Jennum, Andreas Kjær, Steen Gammeltoft
Study objectives: To investigate the activity of brown adipose tissue (BAT) in type 1 narcolepsy patients during cold exposure using two separate scans of sympathetic and metabolic activity of BAT in order to evaluate whether orexin deficiency leads to altered non-shivering thermoregulation in narcolepsy. Methods: Seven patients with type 1 narcolepsy and seven healthy controls underwent two consecutive scans after 2 h cold exposure: 123I-meta-iodo-benzyl-guanidine (123I-MIBG) single photon emission computed tomography and 18F-2-deoxy-glucose (18F-FDG) positron emission tomography and computed tomography to visualize sympathetic innervation and metabolic activity of BAT, respectively...
May 15, 2018: Sleep
https://www.readbyqxmd.com/read/29770600/how-does-glucagon-like-peptide-1-stimulate-human-%C3%AE-cell-proliferation-a-lesson-from-islet-graft-experiments
#14
Yoshio Fujitani
The incidence of type 2 diabetes increases with age. The age-dependent decline in functional β-cell mass contributes to the increased risk of onset of diabetes, reflecting the central role of pancreatic β cells in glucose homeostasis. Indeed, the replication rate of human and rodent β cells is known to decline sharply with age, and such a characteristic of β cells may explain the increased onset of type 2 diabetes in the older population. The molecular mechanism involved in the age-dependent decline of β-cell proliferation has been extensively studied, mainly using rodents and in vitro culture systems, but its molecular basis is still largely unknown...
May 16, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29768729/adaptive-changes-in-pancreas-post-roux-en-y-gastric-bypass-induced-weight-loss
#15
A Lautenbach, M Wernecke, N Riedel, J Veigel, J Yamamura, S Keller, R Jung, P Busch, O Mann, F K Knop, J J Holst, J J Meier, J Aberle
AIMS: Obesity has been shown to trigger adaptive increases in pancreas parenchymal and fat volume. Consecutively, pancreatic steatosis may lead to beta-cell dysfunction. However, it is not known, whether the pancreatic tissue components decrease with weight loss and pancreatic steatosis is reversible following RYGB. Therefore, the objective of the study was to investigate the effects of RYGB-induced weight loss on pancreatic volume and glucose homeostasis. MATERIALS AND METHODS: 11 patients were recruited in the Obesity Centre of the University Medical Centre Hamburg-Eppendorf...
May 16, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29768476/treatment-with-specific-soluble-factors-promotes-the-functional-maturation-of-transcription-factor-mediated-pancreatic-transdifferentiated-cells
#16
Hiroaki Motoyama, Akira Kobayashi, Takahide Yokoyama, Akira Shimizu, Hiroshi Sakai, Tsuyoshi Notake, Kentaro Fukushima, Shin-Ichi Miyagawa
Pancreatic lineage-specific transcription factors (TFs) display instructive roles in converting adult cells to endocrine pancreatic cells through a process known as transdifferentiation. However, little is known about potential factors capable of accelerating transdifferentiation following transduction to achieve the functional maturation of transdifferentiated cells. In this study, we demonstrated, using adult liver-derived progenitor cells, that soluble factors utilized in pancreatic differentiation protocols of pluripotent stem cells promote functional maturation of TFs-mediated transdifferentiated cells...
2018: PloS One
https://www.readbyqxmd.com/read/29765322/therapeutic-potential-of-ginsenosides-as-an-adjuvant-treatment-for-diabetes
#17
REVIEW
Litao Bai, Jialiang Gao, Fan Wei, Jing Zhao, Danwei Wang, Junping Wei
Ginseng, one of the oldest traditional Chinese medicinal herbs, has been used widely in China and Asia for thousands of years. Ginsenosides extracted from ginseng, which is derived from the roots and rhizomes of Panax ginseng C. A. Meyer, have been used in China as an adjuvant in the treatment of diabetes mellitus. Owing to the technical complexity of ginsenoside production, the total ginsenosides are generally extracted. Accumulating evidence has shown that ginsenosides exert antidiabetic effects. In vivo and in vitro tests revealed the potential of ginsenoside Rg1, Rg3, Rg5, Rb1, Rb2, Rb3, compound K, Rk1, Re, ginseng total saponins, malonyl ginsenosides, Rd, Rh2, F2, protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins to treat diabetes and its complications, including type 1 diabetes mellitus, type 2 diabetes mellitus, diabetic nephropathy, diabetic cognitive dysfunction, type 2 diabetes mellitus with fatty liver disease, diabetic cerebral infarction, diabetic cardiomyopathy, and diabetic erectile dysfunction...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29764719/potential-use-of-bitter-melon-momordica-charantia-derived-compounds-as-antidiabetics-in-silico-and-in-vivo-studies
#18
Olusola Olalekan Elekofehinti, Esther Opeyemi Ariyo, Moses Orimoloye Akinjiyan, Olanrewaju Sam Olayeriju, Akeem Olalekan Lawal, Isaac Gbadura Adanlawo, Joao Batista Teixeira Rocha
Momordica charantia (bitter lemon) belongs to the cucurbitaceae family which has been extensively used in traditional medicines for the cure of various ailments such as cancer and diabetes. The underlying mechanism of M. charantia to maintain glycemic control was investigated. GLP-1 and DPP-4 gene modulation by M. charantia (5-20% inclusion in rats diet) was investigated in vivo by RT-PCR and possible compounds responsible for diabetic action predicted through in silico approach. Phytochemicalss previously characterized from M...
May 12, 2018: Pathophysiology: the Official Journal of the International Society for Pathophysiology
https://www.readbyqxmd.com/read/29763559/long-acting-release-microspheres-containing-novel-glp-1-analog-as-an-antidiabetic-system
#19
Sida Ruan, Yuanyuan Gu, Bo Liu, Huashan Gao, Xiongwei Hu, Haiping Hao, Liang Jin, Ting Cai
Glucagon-like peptide 1 (GLP-1) has recently received significant attention as an efficacious way to treat diabetes mellitus. However, the short half-life of the peptide limits its clinical application in diabetes. In our previous study, a novel GLP-1 analog (PGLP-1) with a longer half-life was synthesized and evaluated. Herein, we prepared the PGLP-1-loaded poly(D,L-lactide-co- glycolide) microspheres to achieve long-term effects on blood glucose control. The incorporation of zinc ion into the formulation can effectively decrease the initial burst release, and a uniform drug distribution was obtained, in contrast to native PGLP-1 encapsulated microspheres...
May 15, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29762647/maternal-low-protein-diet-impairs-prostate-growth-in-young-rat-offspring-and-induces-prostate-carcinogenesis-with-aging
#20
Sergio A A Santos, Ana C Camargo, Flávia B Constantino, Ketlin T Colombelli, Fernanda Mani, Jaqueline C Rinaldi, Suelen Franco, Luiz M F Portela, Bruno O S Duran, Wellerson R Scarano, Barry T Hinton, Sergio L Felisbino, Luis A Justulin
Carcinogenesis is frequently linked to genetic background, however, exposure to environmental risk factors has gained attention as the etiologic agent for several types of cancer, including prostate. The intrauterine microenvironment has been described as a preponderant factor for offspring health; and maternal exposure to insult has been linked to chronic disease in older offspring. Using a model of maternal exposure to low protein diet (LPD; 6% protein), we demonstrated that impairment of offspring rat prostatic growth on postnatal day (PND) 21 was associated with prostate carcinogenesis in older offspring (PND 540)...
May 14, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
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