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insulin and GLP-1 analog

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https://www.readbyqxmd.com/read/29200876/effects-of-insulin-analogs-and-glucagon-like-peptide-1-receptor-agonists-on-proliferation-and-cellular-energy-metabolism-in-papillary-thyroid-cancer
#1
Liang He, Siliang Zhang, Xiaowen Zhang, Rui Liu, Haixia Guan, Hao Zhang
Purpose: This study was aimed to investigate the expressions of the insulin receptor (IR), insulin-like growth factor receptor (IGF-1R), and glucagon-like peptide-1 receptor (GLP-1R) in normal thyroid tissue, papillary thyroid cancer (PTC) tissues, and PTC cells, and to examine the possible role of insulin analogs and GLP-1R agonists in cell proliferation and energy metabolism in PTC cells. Methods: The expressions of IR, IGF-1R, and GLP-1R in PTC tissues and PTC cell lines were detected by immunohistochemistry and western blotting, respectively...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29070572/glucagon-like-peptide-1-analog-prevents-obesity-related-glomerulopathy-by-inhibiting-excessive-autophagy-in-podocytes
#2
HongLei Guo, Bin Wang, HongMei Li, LiLu Ling, Jianying Niu, Yong Gu
AIM: To investigate the role of glucagon-like peptide-1 analog (GLP-1) in high fat diet-induced obesity-related glomerulopathy (ORG). METHODS: Male C57BL/6 mice fed a high fat diet for 12 weeks were treated with GLP-1 (200 μg/kg) or 0.9% saline for 4 weeks. Fasting blood glucose and insulin and the expression of podocin, nephrin, phosphoinositide 3-kinase (PI3K), glucose transporter type (Glut4), and microtubule-associated protein 1A/1B-light chain 3 (LC3) were assayed...
October 25, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28867301/nonalcoholic-fatty-liver-disease-as-a-nexus-of-metabolic-and-hepatic-diseases
#3
REVIEW
Varman T Samuel, Gerald I Shulman
NAFLD is closely linked with hepatic insulin resistance. Accumulation of hepatic diacylglycerol activates PKC-ε, impairing insulin receptor activation and insulin-stimulated glycogen synthesis. Peripheral insulin resistance indirectly influences hepatic glucose and lipid metabolism by increasing flux of substrates that promote lipogenesis (glucose and fatty acids) and gluconeogenesis (glycerol and fatty acid-derived acetyl-CoA, an allosteric activator of pyruvate carboxylase). Weight loss with diet or bariatric surgery effectively treats NAFLD, but drugs specifically approved for NAFLD are not available...
August 29, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28767692/insulin-receptor-signaling-and-glucagon-like-peptide-1-effects-on-pancreatic-beta-cells
#4
Nunzia Caporarello, Cristina Parrino, Vincenzo Trischitta, Lucia Frittitta
Glucagon-like peptide-1 (GLP-1) is a potent gluco-incretin hormone, which plays a central role on pancreatic beta cell proliferation, survival and insulin secreting activity and whose analogs are used for treating hyperglycemia in type 2 diabetes mellitus. Notably, abnormal insulin signaling affects all the above-mentioned aspects on pancreatic beta cells. The aim of our study was to investigate whether the protective effects of GLP1-1 on beta cells are affected by altered insulin receptor signaling. To this end, several effects of GLP-1 were studied in INS-1E rat beta cells transfected either with an inhibitor of insulin receptor function (i...
2017: PloS One
https://www.readbyqxmd.com/read/28747330/effects-of-randomized-whey-protein-loads-on-energy-intake-appetite-gastric-emptying-and-plasma-gut-hormone-concentrations-in-older-men-and-women
#5
RANDOMIZED CONTROLLED TRIAL
Caroline Giezenaar, Laurence G Trahair, Natalie D Luscombe-Marsh, Trygve Hausken, Scott Standfield, Karen L Jones, Kylie Lange, Michael Horowitz, Ian Chapman, Stijn Soenen
Background: Protein- and energy-rich supplements are used widely for the management of malnutrition in the elderly. Information about the effects of protein on energy intake and related gastrointestinal mechanisms and whether these differ between men and women is limited.Objective: We determined the effects of whey protein on energy intake, appetite, gastric emptying, and gut hormones in healthy older men and women.Design: Eight older women and 8 older men [mean ± SEM age: 72 ± 1 y; body mass index (in kg/m(2)): 25 ± 1] were studied on 3 occasions in which they received protein loads of 30 g (120 kcal) or 70 g (280 kcal) or a flavored water control drink (0 kcal)...
September 2017: American Journal of Clinical Nutrition
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
#6
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/28609372/pancreatic-polypeptide-cell-proliferation-in-the-pancreas-and-duodenum-coexisting-in-a-patient-with-pancreatic-adenocarcinoma-treated-with-a-glp-1-analog
#7
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/28555111/novel-glp-1-analog-supaglutide-reduces-hfd-induced-obesity-associated-with-increased-ucp-1-in-white-adipose-tissue-in-mice
#8
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/28461341/pglp-1-a-novel-long-acting-dual-function-glp-1-analog-ameliorates-streptozotocin-induced-hyperglycemia-and-inhibits-body-weight-loss
#9
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...
August 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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
#10
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/28336368/novel-strategies-in-the-oral-delivery-of-antidiabetic-peptide-drugs-insulin-glp-1-and-its-analogs
#11
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...
June 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28176959/a-systematic-literature-review-on-the-efficacy-effectiveness-gap-comparison-of-randomized-controlled-trials-and-observational-studies-of-glucose-lowering-drugs
#12
REVIEW
Mikkel Z Ankarfeldt, Erpur Adalsteinsson, Rolf Hh Groenwold, M Sanni Ali, Olaf H Klungel
AIM: To identify a potential efficacy-effectiveness gap and possible explanations (drivers of effectiveness) for differences between results of randomized controlled trials (RCTs) and observational studies investigating glucose-lowering drugs. METHODS: A systematic literature review was conducted in English language articles published between 1 January, 2000 and 31 January, 2015 describing either RCTs or observational studies comparing glucagon-like peptide-1 analogs (GLP-1) with insulin or comparing dipeptidyl peptidase-4 inhibitors (DPP-4i) with sulfonylurea, all with change in glycated hemoglobin (HbA1c) as outcome...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/28176886/assessment-of-channeling-bias-among-initiators-of-glucose-lowering-drugs-a-uk-cohort-study
#13
Mikkel Z Ankarfeldt, Brian L Thorsted, Rolf Hh Groenwold, Erpur Adalsteinsson, M Sanni Ali, Olaf H Klungel
BACKGROUND: Channeling bias may occur when a newly marketed drug and an established drug, despite similar indications, are prescribed to patients with different prognostic characteristics (ie, confounding). AIM: To investigate channeling bias and its impact on relative effectiveness of glucagon-like peptide-1 (GLP-1) analogs versus basal insulin and dipeptidyl peptidase-4 inhibitors (DPP-4i) versus sulfonylurea. METHODS: In the UK Clinical Practice Research Datalink, patients with type 2 diabetes initiating treatment between 2006 and 2015 were included...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/28118069/rationale-for-treatment-options-for-mealtime-glucose-control-in-patients-with-type-2-diabetes
#14
REVIEW
Stephen L Aronoff
While glycemic control is routinely assessed using HbA1c and fasting glucose measures, postprandial glucose (PPG) is also an important contributor of overall glycemia. Furthermore, PPG excursions have been linked to complications of diabetes. This review examines the effects of glucose-lowering therapies (including treatments administered at mealtime) on postprandial hyperglycemia in patients with type 2 diabetes. A PubMed search was conducted to identify clinical studies of treatments for mealtime glucose control in type 2 diabetes...
March 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28098139/appetite-responses-to-high-fat-meals-or-diets-of-varying-fatty-acid-composition-a-comprehensive-review
#15
REVIEW
S Kaviani, J A Cooper
Dietary fatty acids (FA) act as signaling molecules with diverse effects on physiologic function. The aim of this article is to review and summarize the clinical human studies in the literature on how dietary FA composition in meals and diets affects hunger and satiety signaling in the body. Studies examining FA saturation (monounsaturated (MUFA), saturated or polyunsaturated (PUFA) FAs) or FA chain length from high-fat meals/diets were included. Measures of appetite included visual analog scale (VAS) questionnaires, appetite hormones (Cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), gastric insulinotropic polypeptide gastric inhibitory peptide (GIP), ghrelin, leptin, insulin) and/or energy intake (EI) data...
October 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28074109/improvement-of-quality-of-life-through-glycemic-control-by-liraglutide-a-glp-1-analog-in-insulin-naive-patients-with-type-2-diabetes-mellitus-the-page1-study
#16
Hitoshi Ishii, Tetsuji Niiya, Yasuhiro Ono, Naoyuki Inaba, Hideaki Jinnouchi, Hirotaka Watada
BACKGROUND: In addition to achieving good glycemic control, diabetes care management aims to improve the quality of life (QOL) in patients. Treatment-associated difficulties and side effects frequently cause deterioration in QOL. Liraglutide, a GLP-1 receptor agonist, is a novel injection drug that promotes insulin secretion. It is a user-friendly, once-daily injection with fewer hypoglycemic events. In this study, we aimed to examine the effect of liraglutide therapy on QOL in patients...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/28043300/-influences-of-exendin-4-on-the-secretion-function-of-islet-beta-cells-from-rats-in-the-early-stage-of-severe-scald
#17
D X Zhao, L Ma, Z A Shen, D W Li, Y R Shang, K Yin, W F Cheng, X Wang, Z X Liu
Objective: To observe the secretion function changes of islet beta cells isolated from rats in the early stage of severe scald, and to explore the influence of them. Methods: Thirty-six Wistar rats were divided into sham injury (SI) group, sham injury+ exendin-4 (SIE) group, scald (S) group, and scald+ exendin-4 (SE) group according to the random number table, with 9 rats in each group. Rats in groups S and SE were inflicted with 50% total body surface area full-thickness scald by a 12-s immersion of back and a 6-s immersion of abdomen in 94 ℃ hot water...
December 20, 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28036112/protocol-of-glucose-control-safety-and-efficacy-in-type-2-diabetes-a-network-meta-analysis-glucose-dinet-protocol-rational-and-design
#18
REVIEW
Guillaume Grenet, Audrey Lajoinie, Shams Ribault, Gia Bao Nguyen, Thomas Linet, Augustin Metge, Catherine Cornu, Michel Cucherat, Philippe Moulin, François Gueyffier
The aim of this study was to propose a ranking of the currently available antidiabetic drugs, regarding vascular clinical outcomes, in patients with type 2 diabetes, through a network meta-analysis approach. Randomized clinical trials, regardless of the blinding design, testing contemporary antidiabetic drugs, and considering clinically relevant outcomes in patients with type 2 diabetes mellitus will be included. The primary outcomes of this analysis will be overall mortality, cardiovascular mortality, and major cardiovascular events...
December 30, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27965024/a-novel-glp-1-analog-a-dimer-of-glp-1-via-covalent-linkage-by-a-lysine-prolongs-the-action-of-glp-1-in-the-treatment-of-type-2-diabetes
#19
Yingying Pan, Siwei Shi, Xun Lao, Jinlong Zhang, Shiming Tan, Zirong Wu, Jing Huang
GLP-1 is an incretin hormone that can effectively lower blood glucose, however, the short time of biological activity and the side effect limit its therapeutic application. Many methods have been tried to optimize GLP-1 to extend its in vivo half-time, reduce its side effect and enhance its activity. Here we have chosen the idea to dimerize GLP-1 with a C-terminal lysine to form a new GLP-1 analog, DLG3312. We have explored the structure and the biological property of DLG3312, and the results indicated that DLG3312 not only remained the ability to activate the GLP-1R, but also strongly stimulated Min6 cell to secrete insulin...
February 2017: Peptides
https://www.readbyqxmd.com/read/27888738/oxyntomodulin-analog-and-exendin-4-derivative-lower-plasma-glucose-in-cattle
#20
S ThanThan, Y Asada, T Saito, K Ochiiwa, H Zhao, S W Naing, H Kuwayama
The present study was undertaken with the aim of examining whether and how exendin-4 (1-3) fragment, ie, Ex-4 (1-3) fragment, contributes to the regulation of glucose. An analog of oxyntomodulin (OXM) ([Gly(2), Glu(3)]-OXM), a glucagon analog ([Gly(2), Glu(3)]-glucagon), and two derivatives of Ex-4 (glucandin and [Gly(2), Glu(3)]-glucandin) were synthesized by substituting with Gly(2), Glu(3) at the N-terminuses of OXM and glucagon and/or by attaching Ex-4 (30-39) amide at the C-terminus of glucagon. Effects of these peptides on plasma insulin and glucose concentrations were investigated in cattle by conducting 3 in vivo experiments...
November 2, 2016: Domestic Animal Endocrinology
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