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https://www.readbyqxmd.com/read/29233636/amylin-in-alzheimer-s-disease-pathological-peptide-or-potential-treatment
#1
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
#2
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 3-4 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 3-4 weeks of treatment with either pramlintide (8 participants aged 20±3yrs, A1C 6...
December 1, 2017: 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
#3
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...
November 23, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29059473/update-on-the-pharmacology-of-calcitonin-cgrp-family-of-peptides-iuphar-review-x
#4
REVIEW
Debbie L Hay, Michael L Garelja, David R Poyner, Christopher S Walker
The calcitonin/calcitonin gene-related peptide (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 G protein-coupled receptors (GPCRs), the calcitonin receptor (CTR) or the calcitonin receptor-like receptor (CLR). Further diversity arises from heterodimerisation 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)...
October 23, 2017: 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
#5
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
#6
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
#7
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
#8
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
#9
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 to conventional therapy. Yet, reducing glucose excursion as well as simplification of prandial insulin doses remains 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...
July 4, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28672144/zn-ii-pramlintide-stability-binding-sites-and-unexpected-aggregation
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28415672/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...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28363773/amylin-receptor-ligands-reduce-the-pathological-cascade-of-alzheimer-s-disease
#14
Haihao Zhu, Xiehua Xue, Erming Wang, Max Wallack, Hana Na, Jacob M Hooker, Neil Kowall, Qiushan Tao, Thor D Stein, Benjamin Wolozin, Wei Qiao Qiu
Amylin is an important gut-brain axis hormone. Since amylin and amyloid-β peptide (Aβ) share similar β sheet secondary structure despite not having the same primary sequences, we hypothesized that the accumulation of Aβ in the brains of subjects with Alzheimer's disease (AD) might compete with amylin for binding to the amylin receptor (AmR). If true, adding exogenous amylin type peptides would compete with Aβ and reduce the AD pathological cascade, improving cognition. Here we report that a 10-week course of peripheral treatment with human amylin significantly reduced multiple different markers associated with AD pathology, including reducing levels of phospho-tau, insoluble tau, two inflammatory markers (Iba1 and CD68), as well as cerebral Aβ...
June 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28245771/current-drug-targets-in-obesity-pharmacotherapy-a-review
#15
Sangeeta P Bhat, Arun Sharma
Obesity, an impending global pandemic, is not being effectively controlled by current measures such as lifestyle modifications, bariatric surgery or available medications. Its toll on health and economy compels us to look for more effective measures. Fortunately, the advances in biology and molecular technology have been in our favour for delineating new pathways in the pathophysiology of obesity and have led to subsequent development of new drug targets. Development of anti-obesity drugs has often been riddled with problems in the past...
February 27, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28241453/synthesis-of-reusable-silica-nanosphere-supported-pt-iv-complex-for-formation-of-disulfide-bonds-in-peptides
#16
Xiaonan Hou, Xiaowei Zhao, Yamei Zhang, Aiying Han, Shuying Huo, Shigang Shen
Some peptide-based drugs, including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one intramolecular disulfide bond. A novel and reusable monodispersed silica nanosphere-supported Pt(IV) complex (SiO₂@TPEA@Pt(IV)); TPEA: N-[3-(trimethoxysilyl)propyl]ethylenediamine) was synthesized via a four-step procedure and was used for the formation of intramolecular disulfide bonds in peptides. Transmission electron microscopy (TEM) and chemical mapping results for the Pt(II) intermediates and for SiO₂@TPEA@Pt(IV) show that the silica nanospheres possess a monodisperse spherical structure and contain uniformly-distributed Si, O, C, N, Cl, and Pt...
February 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28223444/basal-glucose-can-be-controlled-but-the-prandial-problem-persists-it-s-the-next-target
#17
REVIEW
Matthew C Riddle
Both basal and postprandial elevations contribute to the hyperglycemic exposure of diabetes, but current therapies are mainly effective in controlling the basal component. Inability to control postprandial hyperglycemia limits success in maintaining overall glycemic control beyond the first 5 to 10 years after diagnosis, and it is also related to the weight gain that is common during insulin therapy. The "prandial problem"-comprising abnormalities of glucose and other metabolites, weight gain, and risk of hypoglycemia-deserves more attention...
March 2017: Diabetes Care
https://www.readbyqxmd.com/read/28118069/rationale-for-treatment-options-for-mealtime-glucose-control-in-patients-with-type-2-diabetes
#18
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/28097882/antidiabetic-agents-and-cardiovascular-outcomes-in-patients-with-heart-diseases
#19
Judy W M Cheng, Hisham A Badreldin, Dhiren K Patel, Snehal H Bhatt
INTRODUCTION: This article reviews evidence of the benefits and risk of antidiabetic agents in cardiovascular (CV) outcomes, with a focus on medications approved by the FDA since 2008. STUDY SELECTION: Peer-reviewed articles were identified from MEDLINE and Current Content databases (both 1966 to 1 October 2016) using the search terms insulin, metformin, rosiglitazone, pioglitazone, glyburide, glipizide, glimepiride, acarbose, miglitol, albiglutide, exenatide, liraglutide, lixisenatide, dulaglutide, pramlintide, meglitinide, alogliptin, linagliptin, saxagliptin, sitagliptin, canagliflozin, dapagliflozin, empagliflozin, colesevalam, bromocriptine, mortality, myocardial infarction (MI), heart failure (HF), and stroke...
June 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28093996/challenges-related-to-glycemic-control-in-type-2-diabetes-mellitus-patients
#20
Masoumeh Kheirandish, Hamidreza Mahboobi, Maryam Yazdanparast, Mohammad Amjad Kamal
Diabetes mellitus (DM) is a chronic disease with long-term complications. Glycemic control is an important part in management of DM. The first line in treatment of type 2 DM (T2DM) is diet and life style change. Metformin is the first choice of medication in T2DM patients. Sulfonylureas have high risk of hypoglycemia. Glinides are associated with lower risk of hypoglycemia in comparison to sulfonylureas. Also α-glucosidase inhibitors decrease the polysacarides digestion in small intestine and less effective in comparison to metformin and sulfonylureas in lowering hemoglobin A1c (HbA1c)...
January 15, 2017: Current Drug Metabolism
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