Background And Aims: Due to the unavailability of biologic porcine secretin (BPS), 2 synthetic forms of secretin were developed. Our aim is to determine the bioequivalency of the 3 forms of secretin in pancreatic function testing.
Methods: In a randomized, crossover design, synthetic porcine (SPS) and synthetic human secretin (SHS) were compared in a group of 12 subjects with chronic pancreatitis undergoing secretin stimulation test (SST). The 2 synthetic forms of secretin were then compared with BPS in 12 subjects utilizing a similar design. Finally, 18 healthy subjects underwent secretin stimulation testing with SHS.
Results: There was excellent correlation of peak bicarbonate measurements in the comparison of SPS to SHS (R = 0.967) as well as in the comparison of all 3 forms of secretin (P = 0.08, ANOVA for correlated samples). In the SST, each of the synthetic forms of secretin were 100% accurate in diagnosing chronic pancreatitis in disease subjects and in excluding chronic pancreatitis in normal controls. The synthetic forms of secretin were associated with fewer side effects when compared with BPS with the exception of transient tachycardia which occurred in up to 19% of subjects.
Conclusions: The synthetic porcine and human forms of secretin are equivalent to one another and to biologic porcine secretin and can be used interchangeably in pancreatic function testing.
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http://dx.doi.org/10.1097/00006676-200310000-00006 | DOI Listing |
Nat Commun
October 2024
Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT, 06536, USA.
Type IV pili (T4P) produced by the pathogen Pseudomonas aeruginosa play a pivotal role in adhesion, surface motility, biofilm formation, and infection in humans. Despite the significance of T4P as a potential therapeutic target, key details of their dynamic assembly and underlying molecular mechanisms of pilus extension and retraction remain elusive, primarily due to challenges in isolating intact T4P machines from the bacterial cell envelope. Here, we combine cryo-electron tomography with subtomogram averaging and integrative modelling to resolve in-situ architectural details of the dynamic T4P machine in P.
View Article and Find Full Text PDFAm J Physiol Endocrinol Metab
November 2024
Diabetes, Obesity and Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States.
The secretin-like, class B1 subfamily of seven transmembrane-spanning G protein-coupled receptors (GPCRs) consists of 15 members that coordinate important physiological processes. These receptors bind peptide ligands and use a distinct mechanism of activation that is driven by evolutionarily conserved structural features. For the class B1 receptors, the C-terminus of the cognate ligand is initially recognized by the receptor via an N-terminal extracellular domain that forms a hydrophobic ligand-binding groove.
View Article and Find Full Text PDFJ Neurol Surg B Skull Base
August 2024
Department of Neurosurgery, University of Florida, Gainesville, Florida, United States.
Pituitary neuroendocrine tumors (PitNETs) are rare skull base tumors which can impart significant disability owing to their locally invasive potential. To date, the gamut of PitNET subtypes remains ill-understood at the ligand-receptor (LR) interactome level, potentially limiting therapeutic options. Here, we present findings from in silico analysis of LR complexes formed by PitNETs with clinical presentations of acromegaly, Cushing's disease, high prolactin production, and without symptoms of hormone hypersecretion.
View Article and Find Full Text PDFCell Mol Biol Lett
January 2024
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, PO Box 2040, 3000CA, Rotterdam, The Netherlands.
Background: Loss of CFTR-dependent anion and fluid secretion in the ducts of the exocrine pancreas is thought to contribute to the development of pancreatitis, but little is known about the impact of inflammation on ductal CFTR function. Here we used adult stem cell-derived cell cultures (organoids) obtained from porcine pancreas to evaluate the effects of pro-inflammatory cytokines on CFTR function.
Methods: Organoids were cultured from porcine pancreas and used to prepare ductal epithelial monolayers.
Mol Microbiol
February 2024
Department of Ecophysiology, Max Planck Institute for Terrestrial Microbiology, Marburg, Germany.
In animal pathogens, assembly of the type III secretion system injectisome requires the presence of so-called pilotins, small lipoproteins that assist the formation of the secretin ring in the outer membrane. Using a combination of functional assays, interaction studies, proteomics, and live-cell microscopy, we determined the contribution of the pilotin to the assembly, function, and substrate selectivity of the T3SS and identified potential new downstream roles of pilotin proteins. In absence of its pilotin SctG, Yersinia enterocolitica forms few, largely polar injectisome sorting platforms and needles.
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