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GLP-1 analogs

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https://www.readbyqxmd.com/read/28609372/pancreatic-polypeptide-cell-proliferation-in-the-pancreas-and-duodenum-coexisting-in-a-patient-with-pancreatic-adenocarcinoma-treated-with-a-glp-1-analog
#1
Geoffrey A Talmon, J David Wren, Christophe L Nguyen, Parviz M Pour
A partial pancreaticogastrodudenectomy was performed on a 66-year old man with type 2 diabetes mellitus because of an invasive, moderately differentiated adenocarcinoma in the head of the pancreas. In the adjacent grossly normal tissue of the uncinate process, there was a massive proliferation of pancreatic polypeptide (PP) cells confined to this region and showed invasive pattern. Strikingly, in the heaped area of his duodenum, there was a strikingly large number of PP, glucagon, a few insulin cells in a mini-islet-like patterns composed of glucagon and insulin cells...
July 2017: Pancreas
https://www.readbyqxmd.com/read/28598027/a-novel-gip-analog-zp4165-enhances-glp-1-induced-body-weight-loss-and-improves-glycemic-control-in-rodents
#2
P K Nørregaard, M A Deryabina, P Tofteng Shelton, J U Fog, J R Daugaard, P Eriksson, L F Larsen, L Jessen
AIM: To investigate the effects of the novel GIP analog, ZP4165, on body weight and glycemic control in rodents. Additionally, to investigate if ZP4165 modulates the anti-obesity and anti-hyperglycemic effects of a GLP-1 agonist (liraglutide). METHODS: The acute insulinotropic effect of ZP4165 was investigated in rats during an oral glucose tolerance test. Long-term effects of ZP4165 on body weight and glycemic control, either alone or in combination with liraglutide, were assessed in diet-induced obese mice and diabetic db/db mice...
June 9, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28555111/novel-glp-1-analog-supaglutide-reduces-hfd-induced-obesity-associated-with-increased-ucp-1-in-white-adipose-tissue-in-mice
#3
Yun Wan, Xi Bao, Jiabao Huang, Xiangyu Zhang, Wenjuan Liu, Qiaoli Cui, Dongdong Jiang, Zhihong Wang, Rui Liu, Qinghua Wang
GLP-1, an important incretin hormone plays an important role in the regulation of glucose homeostasis. However, the therapeutic use of native GLP-1 is limited due to its short half-life. We recently developed a novel GLP-1 mimetics (supaglutide) by genetically engineering recombinant fusion protein production techniques. We demonstrated that this formulation possessed long-lasting GLP-1 actions and was effective in glycemic control in both type 1 and type 2 diabetes rodent models. Here, we investigated the effects of supaglutide in regulating energy homeostasis in obese mice...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28554726/microbial-expression-of-exendin-4-analog-and-its-efficacy-in-mice-model
#4
Bhargav Prasad Kodaganti, Pavithra Mukunda, Pravinkumar Dakshinamurthy, Yogendra Manjunath, Bharath Ravindra Shenoy, Veeresha Kamanagowda, Bairavabalakumar Natarajan, Amol Maliwalave, Divya Unnikrishnan, Sathyabalan Murugesan, Vivek Halan, Maloy Ghosh, Sunit Maity
Exendin-4 is a GLP 1 agonist incretin-mimetic peptide hormone comprising 39 amino acids. Exenatide (Byetta(®)) is a chemically synthesized version of Exendin-4 with an additional C-terminal amidation. Exenatide acts as a GLP-1 receptor agonist. This paper illustrates the method adopted for cloning, fermentation and purification of recombinant Exendin-4 analog expressed in Escherichia coli. The biologically expressed analog was extensively characterized using different orthogonal methods to confirm their biological activity and physicochemical properties...
May 26, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28540646/the-molecular-mechanism-of-glucagon-like-peptide-1-therapy-in-alzheimer-s-disease-based-on-a-mechanistic-target-of-rapamycin-pathway
#5
Lin Li
The mechanistic target of rapamycin (mTOR) is an important molecule that connects aging, lifespan, energy balance, glucose and lipid metabolism, and neurodegeneration. Rapamycin exerts effects in numerous biological activities via its target protein, playing a key role in energy balance, regulation of autophagy, extension of lifespan, immunosuppression, and protection against neurodegeneration. There are many similar pathophysiological processes and molecular pathways between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM), and pharmacologic agents used to treat T2DM, including glucagon-like peptide-1 (GLP-1) analogs, seem to be beneficial for AD...
May 24, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28533296/glp-1r-as-a-target-for-the-treatment-of-diabetic-retinopathy-friend-or-foe
#6
Rafael Simó, Cristina Hernández
Glucagon-like peptide 1 receptor (GLP-1R) agonists are increasingly being used as treatment for type 2 diabetes. Since the U.S. Food and Drug Administration published recommendations about the cardiovascular safety of new antidiabetes therapies for treating type 2 diabetes in 2008, the results of two outstanding clinical trials using GLP-1R agonists addressing this issue (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation [LEADER] and Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6]) have been published...
June 2017: Diabetes
https://www.readbyqxmd.com/read/28501576/liraglutide-a-glucagon-like-peptide-1-analog-induce-autophagy-and-senescence-in-hepg2-cells
#7
Gabriele Catyana Krause, Kelly Goulart Lima, Henrique Bregolin Dias, Elisa Feller Gonçalves da Silva, Gabriela Viegas Haute, Bruno Souza Basso, Rodrigo Benedetti Gassen, Elisa Simon Marczak, Rafaela Sole Bach Nunes, Jarbas Rodrigues de Oliveira
It has been reported that glucagon-like peptide-1 (GLP-1) agents have been associated with both the increased risk of cancer and inhibition of tumor growth and metastases. The aim of this study is to evaluate the effect of liraglutide on hepatocellular carcinoma cells - HepG2. Cytometry was used to evaluate mechanism related to decreased cell proliferation. Nuclear staining and morphometric analysis were also used to verify the process that was taking place after treatment with liraglutide, and in order to better understand the mechanism, TGF-β1 was performed...
May 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28461341/pglp-1-a-novel-long-acting-dual-function-glp-1-analog-ameliorates-streptozotocin-induced-hyperglycemia-and-inhibits-body-weight-loss
#8
Huashan Gao, Qian Zhao, Ziwei Song, Zhaocong Yang, You Wu, Shanshan Tang, Murad Alahdal, Yanfeng Zhang, Liang Jin
It is well known that glucagon-like peptide 1 (GLP-1) has antidiabetic action. It has 2 distinct functions, an insulinotropic effect dependent on GLP-1 receptor (GLP-1R) and an insulinomimetic effect independent of GLP-1R. However, use of GLP-1 in vivo is limited by its short half-life. Therefore, our lab designed PGLP-1, a novel 2-function candidate peptide as a potential substitute. Using a streptozotocin-induced hyperglycemic mouse model, we demonstrated in vitro and in vivo that PGLP-1 had insulinotropic actions dependent on GLP-1R and insulinomimetic functions independent of GLP-1R...
May 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28460895/lack-of-effect-of-prolonged-treatment-with-liraglutide-on-cardiac-remodeling-in-rats-after-acute-myocardial-infarction
#9
Kasper Kyhl, Jacob Lønborg, Bolette Hartmann, Hannelouise Kissow, Steen Seier Poulsen, Henrik El Ali, Andreas Kjær, Flemming Dela, Thomas Engstrøm, Marek Treiman
Following the acute phase of a myocardial infarction, a set of structural and functional changes evolves in the myocardium, collectively referred to as cardiac remodeling. This complex set of processes, including interstitial fibrosis, inflammation, myocyte hypertrophy and apoptosis may progress to heart failure. Analogs of the incretin hormone glucagon-like peptide 1 (GLP-1) have shown some promise as cardioprotective agents. We hypothesized that a long-acting GLP-1 analog liraglutide would ameliorate cardiac remodeling over the course of 4 weeks in a rat model of non-reperfused myocardial infarction...
April 28, 2017: Peptides
https://www.readbyqxmd.com/read/28450048/liraglutide-alleviates-h2o2-induced-retinal-ganglion-cells-injury-by-inhibiting-autophagy-through-mitochondrial-pathways
#10
Xuefei Ma, Wenjian Lin, Zhenyu Lin, Ming Hao, Xinyuan Gao, Yue Zhang, Hongyu Kuang
Retinal ganglion cells (RGCs), which exist in the inner retina, are the retinal neurons which can be damaged in the early stage of diabetic retinopathy (DR). Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, exerts biological functions by binding the receptor (GLP-1R), the expression of which in RGC-5 cells was first shown by our team in 2012. It was reported that liraglutide prevented retinal neurodegeneration in diabetic subjects. However, the involvement of mechanisms such as autophagy and mitochondrial balance in liraglutide-induced retinal protection is unknown...
June 2017: Peptides
https://www.readbyqxmd.com/read/28440889/a-glucagon-like-peptide-1-analog-liraglutide-improves-visceral-sensation-and-gut-permeability-in-rats
#11
Tsukasa Nozu, Saori Miyagishi, Shima Kumei, Rintaro Nozu, Kaoru Takakusaki, Toshikatsu Okumura
BACKGROUND AND AIM: A glucagon-like peptide-1 (GLP-1) analog, liraglutide, has been reported to block inflammatory somatic pain. We hypothesized that liraglutide attenuates lipopolysaccharide (LPS)- and repeated water avoidance stress (WAS)-induced visceral hypersensitivity and tested the hypothesis in rats. METHODS: The threshold of the visceromotor response (VMR) induced by colonic balloon distention was measured to assess visceral sensation. Colonic permeability was determined in vivo by quantifying the absorbed Evans blue spectrophotometrically, which was instilled in the proximal colon for 15 min...
April 25, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28424924/effects-of-gw002-a-novel-recombinant-human-glucagon-like-peptide-1-glp-1-analog-fusion-protein-on-cho-recombinant-cells-and-bks-db-mice
#12
Wan-Wan Ji, Dong-An Yu, Min Fan, Meng You, You Lu, Er-Bing Li, Ning Xie, Shou-Sheng Yan
AIMS: GLP-1-based strategies have many advantages in treatment of type 2 diabetes mellitus (T2DM), but native GLP-1 has a short half-life in the circulation, which limits its clinical application. The purpose of this study was to evaluate the effects of GW002, a novel recombinant GLP-1 analog fusion protein produced by linking the human GLP-1 analog C-terminus to the N-terminus of human serum albumin via a linker, in vitro and in BKS-db mice. METHODS: To determine whether GW002 can activate the GLP-1 receptor in cells, the level of luciferase expression was evaluated in vitro...
July 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28365524/pancreas-and-liver-uptake-of-new-radiolabeled-incretins-glp-1-and-exendin-4-in-models-of-diet-induced-and-diet-restricted-obesity
#13
Daniele Seo, Bluma Linkowski Faintuch, Erica Aparecida de Oliveira, Joel Faintuch
INTRODUCTION: Radiolabeled GLP-1 and its analog Exendin-4, have been employed in diabetes and insulinoma. No protocol in conventional Diet-Induced Obesity (DIO), and Diet-Restricted Obesity (DRO), has been identified. Aiming to assess pancreatic beta cell uptake in DIO and DRO, a protocol was designed. METHODS: GLP-1-βAla-HYNIC and HYNIC-βAla-Exendin-4 were labeled with technetium-99m. Four Swiss mouse models were adopted: Controls (C), Alloxan Diabetes Controls (ADC), DIO and DRO...
June 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28347868/teneligliptin-a-dipeptidyl-peptidase-4-inhibitor-attenuated-pro-inflammatory-phenotype-of-perivascular-adipose-tissue-and-inhibited-atherogenesis-in-normoglycemic-apolipoprotein-e-deficient-mice
#14
Hotimah Masdan Salim, Daiju Fukuda, Yasutomi Higashikuni, Kimie Tanaka, Yoichiro Hirata, Shusuke Yagi, Takeshi Soeki, Michio Shimabukuro, Masataka Sata
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have various cellular effects that are associated with vascular protection. Here, we examined whether teneligliptin alters the pro-inflammatory phenotype of perivascular adipose tissue (PVAT) and inhibits atherogenesis. METHODS AND RESULTS: Teneligliptin (60mg/kg/day) was administered orally to apolipoprotein-E-deficient (ApoE(-/-)) mice for 20weeks. Teneligliptin significantly inhibited the development of atherosclerosis in the aortic arch compared with vehicle (P<0...
March 24, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28337257/subcutaneous-liraglutide-ameliorates-methylglyoxal-induced-alzheimer-like-tau-pathology-and-cognitive-impairment-by-modulating-tau-hyperphosphorylation-and-glycogen-synthase-kinase-3%C3%AE
#15
Liqin Qi, Zhou Chen, Yanping Wang, Xiaoying Liu, Xiaohong Liu, Linfang Ke, Zhongjie Zheng, Xiaowei Lin, Yu Zhou, Lijuan Wu, Libin Liu
Memory deterioration and synapse damage with accumulation of β-amyloid and hyperphosphorylated tau are hallmark lesions of Alzheimer's disease (AD). Methylglyoxal (MG), a key intermediate of glucose metabolism, is elevated in AD brains and modifies Aβ42, increasing misfolding and leading to the accumulation of senile plaques. Liraglutide, an analog of glucagon-like peptide-1 (GLP-1), is neurotrophic and neuroprotective. However, whether liraglutide can protect against AD-like memory-related deficits and tau hyperphosphorylation caused by MG in vivo is not known...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28336368/novel-strategies-in-the-oral-delivery-of-antidiabetic-peptide-drugs-insulin-glp-1-and-its-analogs
#16
REVIEW
Ruba Ismail, Ildikó Csóka
As diabetes is a complex disorder being a major cause of mortality and morbidity in epidemic rates, continuous research has been done on new drug types and administration routes. Up to now, a large number of therapeutic peptides have been produced to treat diabetes including insulin, glucagon-like peptide-1 (GLP-1) and its analogs. The most common route of administration of these antidiabetic peptides is parenteral. Due to several drawbacks associated with this invasive route, delivery of these antidiabetic peptides by the oral route has been a goal of pharmaceutical technology for many decades...
March 21, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28300673/semi-microbiological-synthesis-of-an-active-lysinoalanine-bridged-analog-of-glucagon-like-peptide-1
#17
Anneke Kuipers, Louwe de Vries, Marcel P de Vries, Rick Rink, Tjibbe Bosma, Gert N Moll
Some modified glucagon-like-peptide-1 (GLP-1) analogs are highly important for treating type 2 diabetes. Here we investigated whether GLP-1 analogs expressed in Lactococcus lactis could be substrates for modification and export by the nisin dehydratase and transporter enzyme. Subsequently we introduced a lysinoalanine by coupling a formed dehydroalanine with a lysine and investigated the structure and activity of the formed lysinoalanine-bridged GLP-1 analog. Our data show: (i) GLP-1 fused to the nisin leader peptide is very well exported via the nisin transporter NisT, (ii) production of leader-GLP-1 via NisT is higher than via the SEC system, (iii) leader-GLP-1 exported via NisT was more efficiently dehydrated by the nisin dehydratase NisB than when exported via the SEC system, (iv) individual serines and threonines in GLP-1 are dehydrated by NisB to a significantly different extent, (v) an introduced Ser30 is well dehydrated and can be coupled to Lys34 to form a lysinoalanine-bridged GLP-1 analog, (vi) a lysinoalanine(30-34) variant's conformation shifts in the presence of 25% trifluoroethanol towards a higher alpha helix content than observed for wild type GLP-1 under identical condition, (vii) a lysinoalanine(30-34) GLP-1 variant has retained significant activity...
May 2017: Peptides
https://www.readbyqxmd.com/read/28295000/current-status-of-radiopharmaceuticals-for-the-theranostics-of-neuroendocrine-neoplasms
#18
REVIEW
Melpomeni Fani, Petra Kolenc Peitl, Irina Velikyan
Nuclear medicine plays a pivotal role in the management of patients affected by neuroendocrine neoplasms (NENs). Radiolabeled somatostatin receptor analogs are by far the most advanced radiopharmaceuticals for diagnosis and therapy (radiotheranostics) of NENs. Their clinical success emerged receptor-targeted radiolabeled peptides as an important class of radiopharmaceuticals and it paved the way for the investigation of other radioligand-receptor systems. Besides the somatostatin receptors (sstr), other receptors have also been linked to NENs and quite a number of potential radiolabeled peptides have been derived from them...
March 15, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28276830/bariatric-surgery-time-to-replace-with-glp-1
#19
Dominic-Luc Webb, Niclas Abrahamsson, Magnus Sundbom, Per M Hellström
Obesity with a body mass index (BMI) over 30 kg/m(2) represents a significant risk for increased morbidity and mortality, with reduced life expectancy of about 10 years. Until now, surgical treatment has been the only effective longterm intervention. The currently standardized method of bariatric surgery, gastric bypass, means that many gastrointestinal peptide hormones are activated, yielding net reductions in appetite and food intake. Among the most important gut peptide hormones in this perspective is glucagon-like peptide-1 (GLP-1), which rises sharply after gastric bypass...
June 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28245463/protective-effects-of-glucagon-like-peptide-1-analog-on-renal-tubular-injury-in-mice-on-high-fat-diet
#20
Honglei Guo, Hongmei Li, Bin Wang, Wei Ding, Lilu Ling, Min Yang, Yong Gu, Jianying Niu
AIMS: The study aimed to investigate the renoprotective effect of glucagon-like peptide-1 (GLP-1) against renal tubular injury in C57BL/6 mice induced by a high-fat diet (HFD). METHODS: Twenty C57BL/6 mice were fed HFD for 12 weeks. Ten of these mice were treated with GLP-1 at 200 µg/kg subcutaneously twice daily for 4 weeks (HFDG group), and the other ten mice received vehicle only (HFD group). Ten mice fed standard rodent chow served as controls (Con group). Body weight, kidney weight, food intake, and systolic blood pressure were measured...
2017: Cellular Physiology and Biochemistry
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