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Pramlintide

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https://www.readbyqxmd.com/read/29731652/adjunctive-therapy-for-glucose-control-in-patients-with-type-1-diabetes
#1
REVIEW
Kira Harris, Cassie Boland, Lisa Meade, Dawn Battise
Type 1 diabetes mellitus (T1DM) is characterized by relative or absolute insulin deficiency. Despite treatment with insulin therapy, glycemic goals are not always met, and insulin therapy is sometimes limited by adverse effects, including hypoglycemia and weight gain. Several adjunctive therapies have been evaluated in combination with insulin in patients with T1DM to improve glycemic control while minimizing adverse effects. Pramlintide, an amylin analog, can improve glycemic control, primarily through lowering postprandial blood glucose levels...
2018: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/29729352/pegylated-prodrugs-of-antidiabetic-peptides-amylin-and-glp-1
#2
Roland Böttger, Daniel Knappe, Ralf Hoffmann
Agonists of the glucagon-like peptide-1 (GLP-1) receptor and analogs of human amylin have been studied for almost two decades due to their therapeutic potential to treat diabetes mellitus and obesity. Both native peptides exhibit unfavorable pharmacokinetics. Even optimized analogs less prone to proteolysis have to be applied at least daily or once-weekly utilizing microsphere formulations or fusion to proteins. Thus, innovative approaches allowing tuning the drug levels to achieve beneficial therapeutic responses and prolonged application intervals are demanded...
May 2, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29551915/pramlintide-an-antidiabetic-is-antineoplastic-in-colorectal-cancer-and-synergizes-with-conventional-chemotherapy
#3
Maha S Al-Keilani, Dua H Alsmadi, Ruba S Darweesh, Karem H Alzoubi
Background: Approximately 90% of patients with metastatic colorectal cancer fail therapy mainly due to resistance. Taking advantage of currently approved agents for treatment of disease conditions other than cancer for the identification of new adjuvant anticancer therapies is highly encouraged. Pramlintide is a parenteral antidiabetic agent that is currently approved for treatment of types 1 and 2 diabetes mellitus. Objectives: To address the antineoplastic potential of pramlintide in colorectal cancer and to evaluate the ability of pramlintide to enhance the cytotoxicity of 5-fluorouracil, oxaliplatin, and irinotecan against colorectal cancer cell lines expressing wild-type and mutant p53...
2018: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/29504049/future-pharmacotherapy-for-obesity-new-anti-obesity-drugs-on-the-horizon
#4
REVIEW
Gitanjali Srivastava, Caroline Apovian
PURPOSE OF REVIEW: Obesity is a global health crisis with detrimental effects on all organ systems leading to worsening disease state and rising costs of care. Persons with obesity failing lifestyle therapies need to be escalated to appropriate pharmacological treatment modalities, medical devices, and/or bariatric surgery if criteria are met and more aggressive intervention is needed. The progression of severe obesity in the patient population coupled with related co-morbidities necessitates the development of novel therapies for the treatment of obesity...
June 2018: Current Obesity Reports
https://www.readbyqxmd.com/read/29480193/pramlintide-the-effects-of-a-single-drug-injection-on-blood-phosphatidylcholine-profile-for-alzheimer-s-disease
#5
Qiushan Tao, Haihao Zhu, Xi Chen, Robert A Stern, Neil Kowall, Rhoda Au, Jan Krzysztof Blusztajn, Wei Qiao Qiu
Studies suggest that a single injection of pramlintide, an amylin analog, induces changes in Alzheimer's disease (AD) biomarkers in the blood of AD mouse models and AD patients. The aim of this study was to examine whether a pramlintide challenge combined with a phosphatidylcholine (PC) profile diagnoses of AD and mild cognitive impairment (MCI) better than PC alone. Non-diabetic subjects with cognitive status were administered a single subcutaneous injection of 60 mcg of pramlintide under fasting condition...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29389581/study-of-forced-degradation-behavior-of-pramlintide-acetate-by-hplc-and-lc-ms
#6
Yu Yuan, Yuan-Bo Li, Zheng-Fu Tai, Yi-Peng Xie, Xu-Feng Pu, Jian Gao
Pramlintide acetate (Symlin® ), a synthetic analogue of the human hormone amylin. It was approved in March 2005 as a subcutaneous injection for the adjunctive treatment of patients who have type 1 or 2 diabetes mellitus. The objective of current investigation was to study the degradation behavior of pramlintide acetate under different ICH recommended stress conditions by HPLC and LC-MS. Pramlintide acetate was subjected to stress conditions of hydrolysis (acidic or alkaline), oxidation, photolysis and thermal decomposition...
January 2018: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/29378867/iapp-and-type-1-diabetes-implications-for-immunity-metabolism-and-islet-transplants
#7
REVIEW
Heather C Denroche, C Bruce Verchere
Islet amyloid polypeptide (IAPP), the main component of islet amyloid in type 2 diabetes and islet transplants, is now recognized as a contributor to beta cell dysfunction. Increasingly, evidence warrants its investigation in type 1 diabetes owing to both its immunomodulatory and metabolic actions. Autoreactive T cells to IAPP-derived epitopes have been described in humans, suggesting that IAPP is an islet autoantigen in type 1 diabetes. In addition, although aggregates of IAPP have not been implicated in type 1 diabetes, they are potent pro-inflammatory stimuli to innate immune cells, and thus, could influence autoimmunity...
February 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29372531/the-toxic-nature-of-murine-amylin-and-the-immune-responsivity-of-pancreatic-islet-to-conformational-antibody-in-mice
#8
Luiza C S Erthal, Luana Jotha-Mattos, Flávio Alves Lara, Sabrina Alves Dos Reis, Bernardo Miguel de Oliveira Pascarelli, Cinthia Melo Costa, Kleber L A Souza, Luís Maurício T R Lima
The human amylin is a pancreatic peptide hormone found in hyperhormonemic state along with insulin in subclinical diabetes. Amylin has been associated with the pathology of type 2 diabetes, particularly due to its ability to assembly into toxic oligomers and amyloid specimens. On the other hand, some variants such as murine amylin has been described as non-amyloidogenic, either in vitro or in vivo. Recent data have demonstrated the amyloid propensity of murine amylin and the therapeutic analogue pramlintide, suggesting a universality for amylin amyloidosis...
January 25, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29233636/amylin-in-alzheimer-s-disease-pathological-peptide-or-potential-treatment
#9
REVIEW
Elizabeth G Mietlicki-Baase
Alzheimer's disease (AD) is a neurodegenerative disease for which we currently lack effective treatments or a cure. The pancreatic peptide hormone amylin has recently garnered interest as a potential pharmacological target for the treatment of AD. A number of studies have demonstrated that amylin and amylin analogs like the FDA-approved diabetes drug pramlintide can reduce amyloid burden in the brain and improve cognitive symptoms of AD. However, other data suggest that amylin may have pathological effects in AD due to its propensity to misfold and aggregate under certain conditions...
December 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29211871/pramlintide-but-not-liraglutide-suppresses-meal-stimulated-glucagon-responses-in-type-1-diabetes
#10
Alfonso Galderisi, Jennifer Sherr, Michelle VanName, Lori Carria, Melinda Zgorski, Eileen Tichy, Kate Weyman, Eda Cengiz, Stuart Weinzimer, William Tamborlane
Context: Postprandial hyperglycemia remains a challenge in type 1 diabetes (T1D) due, in part, to dysregulated increases in plasma glucagon levels after meals. Objective: This study was undertaken to examine whether 3 to 4 weeks of therapy with pramlintide or liraglutide might help to blunt postprandial hyperglycemia in T1D by suppressing plasma glucagon responses to mixed-meal feedings. Design: Two parallel studies were conducted in which participants underwent mixed-meal tolerance tests (MMTTs) without premeal bolus insulin administration before and after 3 to 4 weeks of treatment with either pramlintide (8 participants aged 20 ± 3 years, hemoglobin A1c 6...
March 1, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29203236/amylin-its-role-in-the-homeostatic-and-hedonic-control-of-eating-and-recent-developments-of-amylin-analogs-to-treat-obesity
#11
REVIEW
Christina Neuner Boyle, Thomas Alexander Lutz, Christelle Le Foll
BACKGROUND: Amylin is a pancreatic β-cell hormone that produces effects in several different organ systems. One of its best-characterized effects is the reduction in eating and body weight seen in preclinical and clinical studies. Amylin activates specific receptors, a portion of which it shares with calcitonin gene-related peptide (CGRP). Amylin's role in the control of energy metabolism relates to its satiating effect, but recent data indicate that amylin may also affect hedonic aspects in the control of eating, including a reduction of the rewarding value of food...
February 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29059473/update-on-the-pharmacology-of-calcitonin-cgrp-family-of-peptides-iuphar-review-25
#12
REVIEW
Debbie L Hay, Michael L Garelja, David R Poyner, Christopher S Walker
The calcitonin/CGRP family of peptides includes calcitonin, α and β CGRP, amylin, adrenomedullin (AM) and adrenomedullin 2/intermedin (AM2/IMD). Their receptors consist of one of two GPCRs, the calcitonin receptor (CTR) or the calcitonin receptor-like receptor (CLR). Further diversity arises from heterodimerization of these GPCRs with one of three receptor activity-modifying proteins (RAMPs). This gives the CGRP receptor (CLR/RAMP1), the AM1 and AM2 receptors (CLR/RAMP2 or RAMP3) and the AMY1, AMY2 and AMY3 receptors (CTR/RAMPs1-3 complexes, respectively)...
January 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29029531/efficacy-and-safety-of-pramlintide-injection-adjunct-to-insulin-therapy-in-patients-with-type-1-diabetes-mellitus-a-systematic-review-and-meta-analysis
#13
Yong-Chao Qiao, Wei Ling, Yan-Hong Pan, Yin-Ling Chen, Dan Zhou, Yan-Mei Huang, Xiao-Xi Zhang, Hai-Lu Zhao
AIMS: We aim to assess the efficacy and safety of pramlintide plus insulin therapy in patients with type 1 diabetes. METHODS: We included clinical studies comparing pramlintide plus insulin to placebo plus insulin. Efficacy was reflected by glycemic control and reduction in body weight and insulin use. Safety concerns were hypoglycemia and other adverse events. Subgroup analysis was performed for different doses (30, 60, 90 µg/meal) and durations (≤4, 26, 29, >29 weeks) of the treatment...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28905065/be-positive-optimizing-pramlintide-from-microcanonical-analysis-of-amylin-isoforms
#14
Rafael B Frigori
Amylin, or human islet amyloid polypeptide (hIAPP), is a 37-residue hormone synergistic to insulin and co-secreted with it by β-cells in the pancreas. The deposition of its cytotoxic amyloid fibrils is strongly related to the progression of Type II diabetes (T2D) and islet graft failures. Notably, isoforms from some mammalian species, such as rats (rIAPP) and porcine (pIAPP), present a few key mutations preventing aggregation. This has lead to biotechnological development of drugs for adjunct therapies of T2D, such as pramlintide, a variant of hIAPP inspired by rIAPP whose proline substitutions have β-strand fibril-breaking properties...
September 27, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28774208/moving-beyond-subcutaneous-insulin-the-application-of-adjunctive-therapies-to-the-treatment-of-type-1-diabetes
#15
REVIEW
Kathleen H Ang, Jennifer L Sherr
With the discovery of insulin nearly a century ago, the diagnosis of Type 1 Diabetes (T1D) transformed from a death sentence to a chronic medical condition. Despite the advances that have been made, the vast majority of those living with T1D still struggle to achieve targeted control. Yet, a plethora of agents have been developed to treat those with Type 2 Diabetes. Exploration of how these agents may benefit those with T1D has been an area of intense investigation, especially due to the overweight/obesity epidemic, which now afflicts more than 60% of those living with T1D...
September 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/28708480/optimizing-diabetes-treatment-in-the-presence-of-obesity
#16
REVIEW
Mary Angelynne Esquivel, M Cecilia Lansang
Evidence of a neurophysiologic mechanism that involves hormones from adipocytes, pancreatic islet cells, and the gastrointestinal tract implicated in both obesity and diabetes has led to a search for drugs that not only either target obesity and diabetes or reduce hemoglobin A1c, but also have weight loss as a potential side effect. The authors review medications approved for the treatment of type 2 diabetes mellitus (including pramlintide, also approved for type 1 diabetes) that also have weight loss as a side effect...
July 2017: Cleveland Clinic Journal of Medicine
https://www.readbyqxmd.com/read/28675686/the-challenges-of-achieving-postprandial-glucose-control-using-closed-loop-systems-in-patients-with-type-1-diabetes
#17
REVIEW
Véronique Gingras, Nadine Taleb, Amélie Roy-Fleming, Laurent Legault, Rémi Rabasa-Lhoret
For patients with type 1 diabetes, closed-loop delivery systems (CLS) combining an insulin pump, a glucose sensor and a dosing algorithm allowing a dynamic hormonal infusion have been shown to improve glucose control when compared with conventional therapy. Yet, reducing glucose excursion and simplification of prandial insulin doses remain a challenge. The objective of this literature review is to examine current meal-time strategies in the context of automated delivery systems in adults and children with type 1 diabetes...
February 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28672144/zn-ii-pramlintide-stability-binding-sites-and-unexpected-aggregation
#18
D Łoboda, M Rowińska-Żyrek
Pramlintide is an antidiabetic drug which mimics amylin - a small peptide co-secreted from pancreatic β-cells together with insulin, one of the hallmarks of type 2 diabetes. In the course of the disease, amylin misfolds into small oligomers or to an aggregated β-sheet amyloid fiber. The misfolding mechanism is not yet quite understood, but it is clear that zinc ions play an important role in the process. This work sheds new light on the role of zinc and pramlintide in the course of the disease, giving a detailed description of the Zn(II)-pramlintide complex, in which the metal ion binds to the imidazole of His18 and the amine group of Lys1, imposing a bend in the peptide between these residues...
September 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28528968/amylin-and-its-g-protein-coupled-receptor-a-probable-pathological-process-and-drug-target-for-alzheimer-s-disease
#19
REVIEW
Wei Qiao Qiu
G-protein-coupled receptors (GPCRs) are shown to be involved in Alzheimer's disease (AD) pathogenesis. However, because GPCRs include a large family of membrane receptors, it is unclear which specific GPCR or pathway with rational ligands can become effective therapeutic targets for AD. Amylin receptor (AmR) is a GPCR that mediates several activities, such as improving glucose metabolism, relaxing cerebrovascular structure, modulating inflammatory reactions and potentially enhancing neural regeneration. Recent studies show that peripheral treatments with amylin or its clinical analog, pramlintide, reduced several components of AD pathology, including amyloid plaques, tauopathy, neuroinflammation and other components in the brain, corresponding with improved learning and memory in AD mouse models...
July 25, 2017: Neuroscience
https://www.readbyqxmd.com/read/28503657/an-amylin-analog-used-as-a-challenge-test-for-alzheimer-s-disease
#20
Haihao Zhu, Robert A Stern, Qiushan Tao, Alexandra Bourlas, Maritza D Essis, Meenakshi Chivukula, James Rosenzweig, Devin Steenkamp, Weiming Xia, Gustavo A Mercier, Yorghos Tripodis, Martin Farlow, Neil Kowall, Wei Qiao Qiu
INTRODUCTION: Preclinical studies demonstrate the potential of amylin in the diagnosis of Alzheimer's disease (AD). We aimed to lay the foundation for repurposing the amylin analog and a diabetes drug, pramlintide, for AD in humans. METHODS: We administered a single subcutaneous injection of 60 μg of pramlintide to nondiabetic subjects under fasting conditions. RESULTS: None of the participants developed hypoglycemia after the injection of pramlintide...
January 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
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