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LC-MS/MS based detection of circulating proinsulin derived peptides in patients with altered pancreatic beta cell function

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Foreman, Rachel 
Gribble, Fiona 
Reimann, Frank 
Meek, Claire 


Routine immunoassays for insulin and C-peptide have the potential to cross-react with partially processed proinsulin products, although in healthy patients these are present at such low levels that the interference is insignificant. Elevated concentrations of proinsulin and des-31,32 proinsulin arising from pathological conditions, or injected insulin analogues, however can cause significant assay interferences, complicating interpretation. Clinical diagnosis and management therefore sometimes require methods that can distinguish true insulin and C-peptide from partially processed proinsulin or injected insulin analogues. In this scenario, the high specificity of mass spectrometric analysis offers potential benefit for patient care. A high throughput targeted LC-MS/MS method was developed as a fit for purpose investigation of insulin, insulin analogues, C-peptide and proinsulin processing intermediates in plasma samples from different patient groups. Using calibration standards and bovine insulin as an internal standard, absolute concentrations of insulin and C-peptide were quantified across a nominal human plasma postprandial range and correlated strongly with immunoassay-based measurements. The ability to distinguish between insulin, insulin analogues and proinsulin intermediates in a single extraction is an improvement over existing immunological based techniques, offering the advantage of exact identification of the species being measured. The method promises to aid in the detection of circulating peptides which have previously been overlooked but may interfere with standard insulin and C-peptide immunoassays.



Clinical analysis, Diabetes, Gastrectomy, Insulin, Liquid chromatography mass spectrometry, Quantitation, Humans, Cattle, Animals, Proinsulin, C-Peptide, Chromatography, Liquid, Insulin-Secreting Cells, Tandem Mass Spectrometry, Insulin, Peptides

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Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences

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Novo Nordisk Foundation (NNF19SA058974)
European Foundation for the Study of Diabetes (EFSD) (NNF19SA058974)
Diabetes UK (17/0005712)
Medical Research Council (MC_UU_12012/3)
Medical Research Council (MR/M009041/1)
Wellcome Trust (220271/Z/20/Z)
BBSRC (2124411)
MRC (MC_UU_00014/3)
MRC (MC_UU_00014/5)
Medical Research Council (MC_PC_12012)
BBSRC-DTP European Foundation for the Study of Diabetes Novo Nordisk Foundation Diabetes UK