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Your search keyword '"Bryan Marzullo"' showing total 2 results
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2 results on '"Bryan Marzullo"'

1. LDHB contributes to the regulation of lactate levels and basal insulin secretion in human pancreatic β cells

Author

Federica Cuozzo, Katrina Viloria, Ali H. Shilleh, Daniela Nasteska, Charlotte Frazer-Morris, Jason Tong, Zicong Jiao, Adam Boufersaoui, Bryan Marzullo, Daniel B. Rosoff, Hannah R. Smith, Caroline Bonner, Julie Kerr-Conte, Francois Pattou, Rita Nano, Lorenzo Piemonti, Paul R.V. Johnson, Rebecca Spiers, Jennie Roberts, Gareth G. Lavery, Anne Clark, Carlo D.L. Ceresa, David W. Ray, Leanne Hodson, Amy P. Davies, Guy A. Rutter, Masaya Oshima, Raphaël Scharfmann, Matthew J. Merrins, Ildem Akerman, Daniel A. Tennant, Christian Ludwig, and David J. Hodson

Subjects
CP: Metabolism, Biology (General), QH301-705.5
Abstract

Summary: Using 13C6 glucose labeling coupled to gas chromatography-mass spectrometry and 2D 1H-13C heteronuclear single quantum coherence NMR spectroscopy, we have obtained a comparative high-resolution map of glucose fate underpinning β cell function. In both mouse and human islets, the contribution of glucose to the tricarboxylic acid (TCA) cycle is similar. Pyruvate fueling of the TCA cycle is primarily mediated by the activity of pyruvate dehydrogenase, with lower flux through pyruvate carboxylase. While the conversion of pyruvate to lactate by lactate dehydrogenase (LDH) can be detected in islets of both species, lactate accumulation is 6-fold higher in human islets. Human islets express LDH, with low-moderate LDHA expression and β cell-specific LDHB expression. LDHB inhibition amplifies LDHA-dependent lactate generation in mouse and human β cells and increases basal insulin release. Lastly, cis-instrument Mendelian randomization shows that low LDHB expression levels correlate with elevated fasting insulin in humans. Thus, LDHB limits lactate generation in β cells to maintain appropriate insulin release.

Published
2024
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2. Fine Structure in Isotopic Peak Distributions Measured Using Fourier Transform Ion Cyclotron Resonance Mass Spectrometry: A Comparison between an Infinity ICR Cell and a Dynamically Harmonized ICR Cell

Author

Jingsha Xu, Meng Li, Bryan Marzullo, Christopher A. Wootton, Mark P. Barrow, and Peter B. O’Connor

Subjects
Fourier Analysis, Structural Biology, Calibration, QD, Cyclotrons, QP, Glutathione, Spectroscopy, Mass Spectrometry
Abstract

The fine structure of isotopic peak distributions of glutathione in mass spectra is measured using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) at 12 and 15 T magnetic field, with an infinity cell and a dynamically harmonized cell (DHC) respectively. The resolved peaks in the fine structure of glutathione consist of 2H, 13C, 15N, 17O, 18O, 33S, 34S, 36S, and combinations of them. The positions of the measured fine structure peaks agree with the simulated isotopic distributions with the mass error less than 250 ppb in broadband mode for the infinity cell and no more than 125 ppb with the DHC after internal calibration. The 15 T FT-ICR MS with DHC cell also resolved around 30 isotopic peaks in broadband with a resolving power (RP) of 2 M. In narrowband (m/z 307–313), our current highest RP of 13.9 M in magnitude mode was observed with a 36 s transient length by the 15 T FT-ICR MS with the DHC and 2ω detection on the 15 T offers slightly higher RP (14.8 M) in only 18 s. For the 12 T FT-ICR MS with the infinity cell, the highest RP achieved was 15.6 M in magnitude mode with a transient length of 45 s. Peak decay was observed for low abundance peaks, which could be due to the suppression effects from the most abundant peak, as result of ion cloud Coulombic interactions (space-charge).\ud \ud

Published
2022

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