A5101941684- Diabetes Treatment and Management
- Pancreatic function and diabetes
- Peptidase Inhibition and Analysis
- Neuropeptides and Animal Physiology
- Metabolism, Diabetes, and Cancer
- Cardiac Ischemia and Reperfusion
- Diabetes Management and Research
- Neuroscience and Neuropharmacology Research
- Diet and metabolism studies
- Cardiac Arrest and Resuscitation
- Contact Dermatitis and Allergies
- Regulation of Appetite and Obesity
- Dermatology and Skin Diseases
- Cardiovascular Function and Risk Factors
- Functional Brain Connectivity Studies
- Receptor Mechanisms and Signaling
- Health Sciences Research and Education
- Cannabis and Cannabinoid Research
- Diabetes and associated disorders
- Eicosanoids and Hypertension Pharmacology
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Nitric Oxide and Endothelin Effects
- Nail Diseases and Treatments
- Pain Mechanisms and Treatments
- Cardiac electrophysiology and arrhythmias
United States Military Academy
2024-2025
King's College London
2024-2025
Medical Research Council
2025
Hammersmith Hospital
2025
University College London
2007-2024
South London and Maudsley NHS Foundation Trust
2024
MRC London Institute of Medical Sciences
2024
University of Ulster
2020-2023
Merck & Co., Inc., Rahway, NJ, USA (United States)
2013-2022
Peking University
2022
Glucagon-like peptide 1 (GLP-1), a gut incretin hormone that stimulates insulin secretion, also activates antiapoptotic signaling pathways such as phosphoinositide 3-kinase and mitogen-activated protein kinase in pancreatic insulinoma cells. Since these kinases have been shown to protect against myocardial injury, we hypothesized GLP-1 could directly the heart injury via prosurvival pathways. Both isolated perfused rat whole animal models of ischemia/reperfusion were used, with infarct size...
Introduction Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a type 2 diabetes mellitus (T2DM) treatment with demonstrated weight loss benefits in clinical trials. However, the extent to which real-world patients T2DM achieve clinically meaningful (≥5%) has not been well characterized. Analysis of data suggests adherence injectable GLP-1 RAs is suboptimal and discontinuation following first year therapy poorly Research design methods A retrospective cohort study among initiating RA...
The action of repaglinide, a novel insulin secretagogue, was compared with the sulfonylurea glibenclamide regard to hypoglycemic in vivo, binding betaTC-3 cells, secretion from perifused mouse islets, and capacity stimulate exocytosis by direct interaction secretory machinery single voltage-clamped beta-cells. Two sites were identified: high-affinity repaglinide (KD = 3.6 nmol/l) site having lower affinity for (14.4 one (25 (550 nmol/l). In contrast glibenclamide, (in concentrations as high...
NN2211 is a long-acting, metabolically stable glucagon-like peptide-1 (GLP-1) derivative designed for once daily administration in humans. dose dependently reduced the glycemic levels ob/ob mice, with antihyperglycemic activity still evident 24 h postdose. Apart from an initial reduction food intake, there were no significant differences between and vehicle treatment, body weight was not affected. Histological examination revealed that beta-cell proliferation mass increased significantly...
Liraglutide is a long‐acting GLP‐1 derivative, designed for once daily administration in type II diabetic patients. To investigate the effects of liraglutide on glycemic control and β ‐cell mass rat models deficiencies, studies were performed male Zucker fatty (ZDF) rats 60% pancreatectomized rats. When was dosed s.c. at 150 μ g kg −1 b.i.d. 6 weeks ZDF 6–8 age study start, diabetes development markedly attenuated. Blood glucose approximately 12 m M lower compared to vehicle ( P <0.0002),...
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) regulate islet function after carbohydrate ingestion. Whether incretin hormones are of importance for ingestion noncarbohydrate macronutrients is not known. This study therefore examined integrated hormone responses to pure fat (oleic acid; 0.88 g/kg) or protein (milk egg protein; 2 over 5 h in healthy men, aged 20-25 yr (n=12); plain water served as control. Both intact (active) total GLP-1 GIP levels...
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide are incretin hormones, secreted in response to meal ingestion. The hormones stimulate insulin secretion essential for the maintenance of normal plasma glucose concentrations. Both metabolized quickly by enzyme dipeptidyl peptidase-IV (DPP-IV). It is well known that type-2 diabetic patients have an impaired effect. Therefore, aim present study was investigate DPP-IV activity fasting postprandial state control...
The incretin effect is responsible for the higher insulin response to oral glucose than iv at matching levels. It not known whether this restricted only. aim of study was examine and hormone responses are after vs. challenge a lipid emulsion with triglyceride levels in humans. A (Intralipid) administered orally (3 ml/kg) or (variable infusion rates match ingestion) healthy lean males (n = 12) University Clinical Research Unit. Samples were collected during 300 min. We measured suprabasal...
BackgroundThe degree of physiological responses to individual antipsychotic drugs is unclear in children and adolescents.With network meta-analysis, we aimed investigate the effects various medications on variables adolescents with neuropsychiatric neurodevelopmental conditions. MethodsFor this searched Medline, EMBASE, PsycINFO, Web Science, Scopus from database inception until Dec 22, 2023, included randomised controlled trials comparing antipsychotics placebo or younger than 18 years any...
Abstract The system that regulates insulin secretion from β‐cells in the islet of Langerhans has a capsaicin‐sensitive inhibitory component. As calcitonin gene‐related peptide (CGRP)‐expressing primary sensory fibers innervate islets, and major proportion CGRP‐containing neurons is sensitive to capsaicin, islet‐innervating may represent Here, we examined expression capsaicin receptor, vanilloid type 1 transient receptor potential (TRPV1) CGRP‐expressing pancreatic effect selective...
Monounsaturated fatty acids, such as oleic acid (OA), and certain milk proteins, especially whey protein (WP), have insulinotropic effects can reduce postprandial glycemia. This effect may involve the incretin hormones glucose-dependent polypeptide (GIP) glucagon-like peptide-1 (GLP-1). To explore this, we examined release inactivation of GIP GLP-1 after administration glucose with or without OA WP through gastric gavage in anesthetized C57BL/6J mice. Insulin responses to (75 mg) were 3-fold...
Activation of apoptosis contributes to cardiomyocyte dysfunction and death in diabetic cardiomyopathy. The peptide glucagon-like peptide-1 (GLP-1), a hormone that is the basis emerging therapy for type 2 patients, has cytoprotective actions different cellular models. We investigated whether GLP-1 inhibits HL-1 cardiomyocytes stimulated with staurosporine, palmitate, ceramide. Studies were performed cardiomyocytes. Apoptosis was induced by incubating cells staurosporine (175 nM), palmitate...
Summary Aims Since 2006, DPP ‐4 inhibitors have become established therapy for the treatment of type 2 diabetes. Despite sharing a common mechanism action, considerable chemical diversity exists amongst members inhibitor class, raising question as to whether structural differences may result in differentiated enzyme inhibition and antihyperglycaemic activity. Methods We compared binding properties most commonly used investigated relationship between their inhibitory potency at level acute...
To assess adherence and discontinuation of injectable glucagon-like peptide-1 receptor agonists (GLP-1 RA) at 12 24 months among adult type 2 diabetes mellitus (T2DM) patients in the United States initiating GLP-1 RA using administrative claims-based database, Optum Clinformatics® Data Mart 7.1.A retrospective study was conducted from 01/2009 to 12/2017. Patients were required be continuously enrolled for prior their first prescription. Proportion days covered (PDC) prescription claims ≥0.80...
Nonrodent models of diabetes are needed for practical and physiological reasons. Induction mild insulin-deficient was investigated in male Göttingen minipigs by use streptozotocin (STZ) alone (75, 100, 125 mg/kg) or mg/kg combined with pretreatment nicotinamide (NIA; 0, 20, 67, 150, 230 mg/kg). Use NIA resulted a less steep slope the regression line between fasting plasma glucose changing doses compared STZ [-7.0 +/- 1.4 vs. 29.7 7.0 mM. mg(-1). kg(-1), P < 0.0001]. Intermediate induced...
Objective : It has earlier been demonstrated that capsaicin-induced desensitization improves insulin sensitivity in normal rats. However, whether increased capsaicin-sensitive nerve activity precedes the onset of resistance diet-induced obesity – and therefore might be involved pathophysiology is not known. Further, it relevance to investigate capsaicin glycaemic control even obese individuals we chose Zucker rats test this. Design methods Plasma levels calcitonin gene-related peptide (CGRP;...
A total of 1,832 patients with nonatopic and non-"functional" dermatologic problems were questioned for personal and/or family history atopic disorders. The incidence positive histories was 19.4%, while the atopy 22.6%. Among 1,476 subjects without a 18.4%. Difficulties in establishing satisfactory criteria methods such study are discussed. Previous studies on this problem tabulated. An apparent increase record over years has occurred. We suggest true general population now approximates 20%...
The first non-peptide competitive human glucagon receptor antagonist, 2-(benzimidazol-2-ylthio)-1-(3,4-dihydroxyphenyl)-1-ethan one, NNC 92-1687 (2), is described. This antagonist has a binding affinity of 20 microM (IC50) and functional Ki = 9.1 at the receptor. A structure-activity relationship (SAR) was obtained on this compound, results show that only benzimidazole part can be changed without complete loss affinity. Analogues with tert-butyl or benzyloxy groups in 5-position moiety were...
Repaglinide and nateglinide represent a new class of insulin secretagogues, structurally unrelated to sulphonylureas, that were developed for the treatment type 2 diabetes. The inhibitory effect these drugs was investigated on recombinant wild-type mutant Kir6.2/SUR1 channels expressed in HEK293 cells. Nateglinide repaglinide dose-dependently inhibited whole-cell currents with half-maximal concentration (IC50) values 800 21 nmol/l, respectively. Mutation serine 1237 SUR1 tyrosine (S1237Y)...