Publications
79 results found
Cegla J, Jones BJ, Howard J, et al., 2017, The preanalytical stability of glucagon as measured by liquid chromatography tandem mass spectrometry and two commercially available immunoassays, Annals of Clinical Biochemistry, Vol: 54, Pages: 293-296, ISSN: 1758-1001
BackgroundOne of the main challenges in the measurement of glucagon is the premise that it is unstable in human plasma. Traditionally, protease inhibitors have been used to prevent its degradation; however, their use is controversial. Here, we investigated the optimal method of sample collection for glucagon, with measurement by liquid chromatography tandem mass spectrometry (LC-MS/MS) and two commercially available immunoassays.MethodsBlood from healthy fasting volunteers (n = 10) was processed under a variety of preanalytical conditions including collection in EDTA vs. lithium heparin tubes and the addition of aprotinin and/or a dipeptidyl-peptidase IV (DPPIV) inhibitor. Additionally, the effect of freeze thaw was assessed. Plasma glucagon concentrations were measured by LC-MS/MS and two commercially available immunoassays (HTRF® sandwich immunoassay, Cisbio and Milliplex MAP Human Metabolic Hormone Panel, Merck Millipore).ResultsA systematic bias of Milliplex > LC-MS/MS > HTRF was noted and plasma glucagon concentrations were significantly different between methods (Milliplex vs. LC-MS/MS P < 0.01; Milliplex vs. HTRF P < 0.0001; LC-MS/MS vs. HTRF P < 0.001). The addition of aprotinin, DPPIV inhibitor or a combination of aprotinin and DPPIV inhibitor had no effect on plasma glucagon concentrations when compared to ‘non-stabilized’ samples or each other. Whether samples were taken in EDTA tubes or lithium heparin tubes made no difference to plasma glucagon concentrations. These findings were consistent for all three methods. Plasma glucagon concentrations were not significantly different after two freeze–thaw cycles (performed on samples in EDTA tubes containing aprotinin and DPPIV inhibitor).ConclusionsThis study demonstrates that glucagon is stable in both EDTA and lithium heparin tubes when stored at −80℃. Furthermore, the addition of ap
Broichhagen J, Johnston NR, von Ohlen Y, et al., 2016, Allosteric optical control of a class B G-protein-coupled receptor, Angewandte Chemie - International Edition, Vol: 55, Pages: 5865-5868, ISSN: 1433-7851
Broichhagen J, Podewin T, Meyer-Berg H, et al., 2015, Optical control of insulin secretion using an incretin switch, Angewandte Chemie International Edition, Vol: 54, Pages: 15565-15569, ISSN: 1433-7851
Incretin mimetics are set to become a mainstay of type 2 diabetes treatment. By acting on the pancreas and brain, they potentiate insulin secretion and induce weight loss to preserve normoglycemia. Despite this, incretin therapy has been associated with off-target effects, including nausea and gastrointestinal disturbance. A novel photoswitchable incretin mimetic based upon the specific glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide was designed, synthesized, and tested. This peptidic compound, termed LirAzo, possesses an azobenzene photoresponsive element, affording isomer-biased GLP-1R signaling as a result of differential activation of second messenger pathways in response to light. While the trans isomer primarily engages calcium influx, the cis isomer favors cAMP generation. LirAzo thus allows optical control of insulin secretion and cell survival.
Jones BJ, Bloom SR, 2015, The new era of drug therapy for obesity: The evidence and the expectations, Drugs, Vol: 75, Pages: 935-945, ISSN: 1179-1950
There is an urgent need for effective pharmacological therapies to help tackle the growing obesity epidemic and the healthcare crisis it poses. The past 3 years have seen approval of a number of novel anti-obesity drugs. The majority of these influence hypothalamic appetite pathways via dopaminergic or serotoninergic signalling. Some are combination therapies, allowing lower doses to minimize the potential for off-target effects. An alternative approach is to mimic endogenous satiety signals using long-lasting forms of peripheral appetite-suppressing hormones. There is also considerable interest in targeting thermogenesis by brown adipose tissue to increase resting energy expenditure. Obesity pharmacotherapy has seen several false dawns, but improved understanding of the pathways regulating energy balance, and better-designed trials, give many greater confidence that recently approved agents will be both efficacious and safe. Nevertheless, a number of issues from preclinical and clinical development continue to attract debate, and additional large-scale trials are still required to address areas of uncertainty.
Jones B, 2015, Contemporary bloodletting in cardiac surgical care., Ann Clin Biochem, Vol: 52
Jones B, 2015, Glucagon-like peptide 1 deficiency in type 1 diabetes?, ANNALS OF CLINICAL BIOCHEMISTRY, Vol: 52, Pages: 191-192, ISSN: 0004-5632
Cegla J, Troke RC, Jones B, et al., 2014, Coinfusion of low-dose GLP-1 and glucagon in man results in a reduction in food intake, Diabetes, Vol: 63, Pages: 3711-3720, ISSN: 0012-1797
Obesity is a growing epidemic, and current medical therapies have proven inadequate. Endogenous satiety hormones provide an attractive target for the development of drugs that aim to cause effective weight loss with minimal side effects. Both glucagon and GLP-1 reduce appetite and cause weight loss. Additionally, glucagon increases energy expenditure. We hypothesized that the combination of both peptides, administered at doses that are individually subanorectic, would reduce appetite, while GLP-1 would protect against the hyperglycemic effect of glucagon. In this double-blind crossover study, subanorectic doses of each peptide alone, both peptides in combination, or placebo was infused into 13 human volunteers for 120 min. An ad libitum meal was provided after 90 min, and calorie intake determined. Resting energy expenditure was measured by indirect calorimetry at baseline and during infusion. Glucagon or GLP-1, given individually at subanorectic doses, did not significantly reduce food intake. Coinfusion at the same doses led to a significant reduction in food intake of 13%. Furthermore, the addition of GLP-1 protected against glucagon-induced hyperglycemia, and an increase in energy expenditure of 53 kcal/day was seen on coinfusion. These observations support the concept of GLP-1 and glucagon dual agonism as a possible treatment for obesity and diabetes.
Jones B, 2014, Exploring necrotizing autoimmune myopathies with a novel immunoassay for anti-3-hydroxy-3-methyl-glutaryl-CoA reductase autoantibodies., Ann Clin Biochem, Vol: 51
Cegla J, Jones B, Seyani L, et al., 2013, Comparison of the overnight metyrapone and glucagon stimulation tests in the assessment of secondary hypoadrenalism, CLINICAL ENDOCRINOLOGY, Vol: 78, Pages: 738-742, ISSN: 0300-0664
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- Citations: 14
Jones BJ, Zollner J, Haynes S, et al., 2013, <i>In vitro</i> fertilization treatment influences glucose tolerance in multiple pregnancy, DIABETIC MEDICINE, Vol: 30, Pages: 252-254, ISSN: 0742-3071
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- Citations: 8
Fasano T, Zanoni P, Rabacchi C, et al., 2012, Novel mutations of ABCA1 transporter in patients with Tangier disease and familial HDL deficiency, MOLECULAR GENETICS AND METABOLISM, Vol: 107, Pages: 534-541, ISSN: 1096-7192
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- Citations: 26
Jones BJ, Tan T, Bloom SR, 2012, Minireview: Glucagon in Stress and Energy Homeostasis, ENDOCRINOLOGY, Vol: 153, Pages: 1049-1054, ISSN: 0013-7227
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- Citations: 81
Jones BJ, Twomey PJ, 2009, Comparison of reflective and reflex testing for hypomagnesaemia in severe hypokalaemia, JOURNAL OF CLINICAL PATHOLOGY, Vol: 62, Pages: 816-819, ISSN: 0021-9746
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- Citations: 13
Jones BJ, Twomey PJ, Reynolds T, 2009, Average serum triglyceride concentration in relation to day of the week in Burton-on-Trent, JOURNAL OF CLINICAL PATHOLOGY, Vol: 62, Pages: 671-672, ISSN: 0021-9746
Yalamati P, Jones BJ, Twomey PJ, 2009, Appropriateness of the National Academy of Clinical Biochemistry recommendation of repeating HbA1c analysis for extreme results in clinical practice, ANNALS OF CLINICAL BIOCHEMISTRY, Vol: 46, Pages: 165-166, ISSN: 0004-5632
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- Citations: 1
Jones BJ, Twomey PJ, 2009, Requesting patterns for serum calcium concentration in patients on long-term lithium therapy, INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Vol: 63, Pages: 170-172, ISSN: 1368-5031
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- Citations: 2
Jones BJ, Twomey PJ, 2008, Effect of a manually generated laboratory comment on requesting and performance of valproate assays, JOURNAL OF CLINICAL PATHOLOGY, Vol: 61, Pages: 1231-1231, ISSN: 0021-9746
Twomey PJ, Jones BJ, Pledger DR, 2008, Introduction of automatically generated comment in clinical biochemistry: an audit of technical effectiveness, BRITISH JOURNAL OF BIOMEDICAL SCIENCE, Vol: 65, Pages: 102-103, ISSN: 0967-4845
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- Citations: 1
Hejmadi MV, Dajas-Bailador F, Barns SM, et al., 2003, Neuroprotection by nicotine against hypoxia-induced apoptosis in cortical cultures involves activation of multiple nicotinic acetylcholine receptor subtypes, MOLECULAR AND CELLULAR NEUROSCIENCE, Vol: 24, Pages: 779-786, ISSN: 1044-7431
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- Citations: 88
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