Publications by authors named "Mark Denn"

Daily restricted access to food leads to the development of food anticipatory activity and metabolism, which depends upon an as yet unidentified food-entrainable oscillator(s). A premeal anticipatory peak in circulating hormones, including corticosterone is also elicited by daily restricted feeding. High-fat feeding is associated with elevated levels of corticosterone with disrupted circadian rhythms and a failure to develop robust meal anticipation.

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The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a target for novel type 2 diabetes and obesity therapies based on the premise that lowering of tissue glucocorticoids will have positive effects on body weight, glycemic control, and insulin sensitivity. An 11β-HSD1 inhibitor (compound C) inhibited liver 11β-HSD1 by >90% but led to only small improvements in metabolic parameters in high-fat diet (HFD)-fed male C57BL/6J mice. A 4-fold higher concentration produced similar enzyme inhibition but, in addition, reduced body weight (17%), food intake (28%), and glucose (22%).

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Background: Laser diode thermal desorption (LDTD) is a relatively new sample introduction interface for MS. Analysis times are short as the technique does not require time-consuming separation steps, such as conventional HPLC, thus saving on the use of organic solvents, modifiers and cost, relating to their subsequent disposal. This paper compares the merits of LDTD-APCI-MS/MS and LC-MS/MS for the analysis of paracetamol (acetaminophen) in plasma from different species.

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A simple, rapid and robust high-throughput assay for the simultaneous analysis of metformin and sitagliptin from mouse and human dried blood spot samples using laser diode thermal desorption interfaced with atmospheric pressure chemical ionization tandem mass spectrometry (LDTD-APCI-MS/MS) was developed for use in a pharmaceutical discovery environment as an alternative to traditional plasma analysis. Analytes were extracted from dried blood spots using a simple punch disc and solvent extract procedure. Details of the method development and optimization of the instrumental parameters are presented.

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