0000000000923354
AUTHOR
Stephen O'rahilly
showing 5 related works from this author
Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection
1999
Non-insulin-dependent diabetes mellitus (NIDDM) may be associated with chronic hepatitis C virus (HCV) infection. This was studied further in two parts. First, 1,151 patients with HCV-related cirrhosis and 181 patients with hepatitis B virus (HBV)-related cirrhosis, well matched for age, sex, and severity of cirrhosis, were reviewed retrospectively. The prevalence of diabetes mellitus was higher in HCV-related cirrhosis (23.6%) than in HBV-related cirrhosis (9.4%; odds ratio [OR], 2.78; 95% confidence interval [CI], 1.6-4.79; P =.0002). The prevalence of diabetes mellitus was associated closely with the Child-Pugh score (OR, 3.83; 95% CI, 2. 38-6.17; P.0001) and increasing age (OR, 1.02; 95…
Human POMC processing in vitro and in vivo revealed by quantitative peptidomics
2018
ABSTRACTHuman obesity can result from the aberrant production or processing of proopiomelanocortin (POMC) in hypothalamic neurons, but it is unclear which human POMC-derived peptides are most relevant to body weight regulation. To address this question, we analysed both hypothalamic neurons derived from human pluripotent stem cells (hPSCs) and primary human hypothalamic tissue using quantitative liquid chromatography tandem mass spectroscopy (LC-MS/MS). In both in vitro- and in vivo-derived samples, we found that POMC was processed into β-melanocyte stimulating hormone (β-MSH), whose existence in the human brain has been controversial. β-MSH and desacetyl α-MSH (d-α-MSH) were produced at ro…
An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.
2016
Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub…
Quantitative mass spectrometry for human melanocortin peptides in vitro and in vivo suggests prominent roles for b-MSH and desacetyl a-MSH in energy …
2018
Objective: The lack of pro-opiomelanocortin (POMC)-derived melanocortin peptides results in hypoadrenalism and severe obesity in both humans and rodents that is treatable with synthetic melanocortins. However, there are significant differences in POMC processing between humans and rodents, and little is known about the relative physiological importance of POMC products in the human brain. The aim of this study was to determine which POMC-derived peptides are present in the human brain, to establish their relative concentrations, and to test if their production is dynamically regulated. Methods: We analysed both fresh post-mortem human hypothalamic tissue and hypothalamic neurons derived fro…
Quantitative mass spectrometry for human melanocortin peptides in vitro and in vivo suggests prominent roles for β-MSH and desacetyl α-MSH in energy …
2018
Objective The lack of pro-opiomelanocortin (POMC)-derived melanocortin peptides results in hypoadrenalism and severe obesity in both humans and rodents that is treatable with synthetic melanocortins. However, there are significant differences in POMC processing between humans and rodents, and little is known about the relative physiological importance of POMC products in the human brain. The aim of this study was to determine which POMC-derived peptides are present in the human brain, to establish their relative concentrations, and to test if their production is dynamically regulated. Methods We analysed both fresh post-mortem human hypothalamic tissue and hypothalamic neurons derived from …