A5042517216- Pancreatic function and diabetes
- Diabetes Treatment and Management
- Metabolism, Diabetes, and Cancer
- Diabetes Management and Research
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Lipoproteins and Cardiovascular Health
- Diabetes and associated disorders
- Calcium signaling and nucleotide metabolism
- Diet, Metabolism, and Disease
- Neuroscience and Neuropharmacology Research
- Cancer, Lipids, and Metabolism
- Adipose Tissue and Metabolism
- Ion channel regulation and function
- Nitric Oxide and Endothelin Effects
- Neuropeptides and Animal Physiology
- Gastrointestinal disorders and treatments
- Cannabis and Cannabinoid Research
- Neuroendocrine Tumor Research Advances
- Adenosine and Purinergic Signaling
- Atrial Fibrillation Management and Outcomes
- Receptor Mechanisms and Signaling
- Neurological disorders and treatments
- Electron Spin Resonance Studies
Oxford Centre for Diabetes, Endocrinology and Metabolism
2010-2023
Churchill Hospital
2010-2023
University of Oxford
2010-2023
Kawasaki Medical School
2004-2015
Kawasaki Medical School Hospital
2006-2009
Yanagawa Rehabilitation Hospital
1964
The majority of genetic risk variants for type 2 diabetes (T2D) affect insulin secretion, but the mechanisms through which they influence pancreatic islet function remain largely unknown. We functionally characterized human islets to determine secretory, biophysical, and ultrastructural features in relation profiles diabetic nondiabetic donors. Islets from donors with T2D exhibited impaired was more pronounced lean than obese assessed impact 14 disease susceptibility on measures glucose...
Strategies aimed at mimicking or enhancing the action of incretin hormone glucagon-like peptide 1 (GLP-1) therapeutically improve glucose-stimulated insulin secretion (GSIS); however, it is not clear whether GLP-1 directly drives in pancreatic islets. Here, we examined mechanisms by which stimulates mouse and human We found that enhances GSIS a half-maximal effective concentration 0.4 pM. Moreover, determined activates PLC, increases submembrane diacylglycerol thereby PKC, resulting membrane...
To document the properties of voltage-gated ion channels in human pancreatic alpha-cells and their role glucagon release.Glucagon release was measured from intact islets. [Ca(2+)](i) recorded cells showing spontaneous activity at 1 mmol/l glucose. Membrane currents potential were by whole-cell patch-clamping isolated identified immunocytochemistry.Glucose inhibited secretion islets; maximal inhibition observed 6 Glucagon glucose insulin but not ZnCl(2). Glucose remained inhibitory presence...
Glucagon is the body's main hyperglycemic hormone, and its secretion dysregulated in type 2 diabetes mellitus (T2DM). The incretin hormone glucagon-like peptide-1 (GLP-1) released from gut used T2DM therapy. Uniquely, it both stimulates insulin inhibits glucagon thereby lowers plasma glucose levels. In this study, we have investigated action of GLP-1 on release human pancreatic islets. Immunocytochemistry revealed that only <0.5% α-cells possess detectable GLP-1R immunoreactivity. Despite...
Abstract Aims/hypothesis Diabetes mellitus is associated with impaired insulin secretion, often aggravated by oversecretion of glucagon. Therapeutic interventions should ideally correct both defects. Glucagon-like peptide 1 (GLP-1) has this capability but exactly how it exerts its glucagonostatic effect remains obscure. Following release GLP-1 rapidly degraded from GLP-1(7–36) to GLP-1(9–36). We hypothesised that the metabolite GLP-1(9–36) (previously believed be biologically inactive) a...
Nateglinide and mitiglinide (glinides) are characterized as rapid-onset short-acting insulinotropic agents. Although both compounds do not have a sulfonylurea structure, it has been postulated that insulin secretion is preceded by their binding to Kir6.2/SUR1 complex, mechanism of glinides accounted for this pathway. However, we hypothesized the involvement additional mechanisms enhanced glinides, analyzed pattern time course from MIN6 cells with existence agents specific pharmacologic...
OBJECTIVE—The aim of this study was to investigate the effect apolipoprotein (apo)E4 allele on plasma LDL cholesterol response calorie-restricted diet therapy in type 2 diabetic patients. RESEARCH DESIGN AND METHODS—Twenty-four patients with apoE3/3 genotype and 11 apoE4/3 were recruited. Participants hospitalized for (25.0 kcal · kg body wt−1 day−1) 14 days. Body weight, fasting glucose (FPG) levels, lipid levels hospital days 1 compared between two apoE groups. RESULTS—There no significant...
Summary The incretin hormone glucagon-like peptide 1(7-36) (GLP-1(7-36)) stimulates insulin and inhibits glucagon secretion. mechanisms by which GLP-1 suppresses release are unclear as glucagon-secreting α-cells express receptors (GLP-1Rs) at very low levels. Here, we examine the underlying mechanisms. We find that both GLP-1(7-36) its degradation product GLP-1(9-36) inhibit secretion physiological (pM) concentrations. Whereas effect of is sensitive to PKA inhibition, exerts a...
Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone classified as incretin. GLP-1 secreted from L-cells, which are located in the lower gastrointestinal tract, by stimulation of several kinds nutrition, such carbohydrate. transported to pancreas probably through bloodstream and nervous system, not only regulates pancreatic hormones, but also involved differentiation, proliferation regulation β-cell mass. inactivated dipeptidil peptidase-IV (DPP-IV) a rapid manner. receptor agonists...
A 29-year-old woman was diagnosed as having type 1 diabetes mellitus and received insulin aspart NPH (NovolinN). On day 22, she had leg edema right abdominal pain. The serum hepatobiliary enzyme levels were markedly elevated. Computed tomography revealed gallbladder edema. After an injection of human regular (HumacartN), the elevated liver no longer observed. Challenge testing demonstrated that protamine cause her allergy. Furthermore, tests increased VEGF levels. This is extremely rare case...
Abstract We investigated a role of nitric oxide (NO) on ionomycin‐evoked [ 3 H]GABA release using mouse cerebral cortical neurons. Ionomycin dose‐dependently released up to 1 µ m . The extent the by 0.1 ionomycin was in range similar that 30 KCl. (0.1 )‐evoked inhibited NO synthase inhibitors and hemoglobin, indicating is mediated through formation. inhibition cGMP formation H ‐[1,2,4] oxodizao [4,3‐a] quinoxalin‐1‐one (ODQ), selective inhibitor for NO‐sensitive guanylate cyclase, showed no...